Phosphatidylcholine Biosynthesis via CTP:Phosphocholine Cytidylyltransferase β2 Facilitates Neurite Outgrowth and Branching

Hallmarks of neuronal differentiation are neurite sprouting, extension, and branching. We previously showed that increased expression of CTP:phosphocholine cytidylyltransferase β2 (CTβ2), an isoform of a key phosphatidylcholine (PC) biosynthetic enzyme, accompanies neurite outgrowth (Carter, J. M., Waite, K. A., Campenot, R. B., Vance, J. E., and Vance, D. E. (2003) J. Biol. Chem. 278, 44988–44994). CTβ2 mRNA is highly expressed in the brain. We show that CTβ2 is abundant in axons of rat sympathetic neurons and retinal ganglion cells. We used RNA silencing to decrease CTβ2 expression in PC12 cells differentiated by nerve growth factor. In CTβ2-silenced cells, numbers of primary and secondary neurites were markedly reduced, suggesting that CTβ2 facilitates neurite outgrowth and branching. However, the length of individual neurites was significantly increased, and the total amount of neuronal membrane was unchanged. Neurite branching of PC12 cells is known to be inhibited by activation of Akt and promoted by the Akt inhibitor LY294002. Our experiments showed that LY294002 increases neurite sprouting and branching in control PC12 cells but not in CTβ2-deficient cells. CTβ2 was not phosphorylated in vitro by Akt. However, inhibition of Cdk5 by roscovitine blocked CTβ2 phosphorylation and reduced neurite outgrowth and branching. These results highlight the importance of CTβ2 in neurons for promoting neurite outgrowth and branching and represent the first identification of a lipid biosynthetic enzyme that facilitates these functions. Hallmarks of neuronal differentiation are neurite sprouting, extension, and branching. We previously showed that increased expression of CTP:phosphocholine cytidylyltransferase β2 (CTβ2), an isoform of a key phosphatidylcholine (PC) biosynthetic enzyme, accompanies neurite outgrowth (Carter, J. M., Waite, K. A., Campenot, R. B., Vance, J. E., and Vance, D. E. (2003) J. Biol. Chem. 278, 44988–44994). CTβ2 mRNA is highly expressed in the brain. We show that CTβ2 is abundant in axons of rat sympathetic neurons and retinal ganglion cells. We used RNA silencing to decrease CTβ2 expression in PC12 cells differentiated by nerve growth factor. In CTβ2-silenced cells, numbers of primary and secondary neurites were markedly reduced, suggesting that CTβ2 facilitates neurite outgrowth and branching. However, the length of individual neurites was significantly increased, and the total amount of neuronal membrane was unchanged. Neurite branching of PC12 cells is known to be inhibited by activation of Akt and promoted by the Akt inhibitor LY294002. Our experiments showed that LY294002 increases neurite sprouting and branching in control PC12 cells but not in CTβ2-deficient cells. CTβ2 was not phosphorylated in vitro by Akt. However, inhibition of Cdk5 by roscovitine blocked CTβ2 phosphorylation and reduced neurite outgrowth and branching. These results highlight the importance of CTβ2 in neurons for promoting neurite outgrowth and branching and represent the first identification of a lipid biosynthetic enzyme that facilitates these functions. In response to nerve growth factor (NGF), 6The abbreviations used are:NGFnerve growth factorCTCTP:phosphocholine cytidylyltransferaseGFPgreen fluorescent proteinHAhemagglutininPCphosphatidylcholinesiRNAsmall interfering RNA rat pheochromocytoma (PC12) cells stop proliferating and differentiate into sympathetic neuron-like cells (1Greene L.A. Tischler A.S. Proc. Natl. Acad. Sci. U. S. A. 1976; 73: 2424-2428Crossref PubMed Scopus (4873) Google Scholar). The morphological hallmark of neuronal differentiation is neurite sprouting and elongation and subsequent maturation of neurites into axons and dendrites. These processes increase the demand for membrane components. Accordingly, the biosynthesis of the predominant membrane phospholipid, phosphatidylcholine (PC), is accelerated during neurite outgrowth in response to NGF (2Araki W. Wurtman R.J. Proc. Natl. Acad. Sci. U. S. A. 1997; 94: 11946-11950Crossref PubMed Scopus (75) Google Scholar, 3Carter J.M. Waite K.A. Campenot R.B. Vance J.E. Vance D.E. J. Biol. Chem. 2003; 278: 44988-44994Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar). nerve growth factor CTP:phosphocholine cytidylyltransferase green fluorescent protein hemagglutinin phosphatidylcholine small interfering RNA PC is synthesized in neurons by the CDP-choline pathway (4Vance J.E. Pan D. Campenot R.B. Bussiere M. Vance D.E. J. Neurochem. 1994; 62: 329-337Crossref PubMed Scopus (94) Google Scholar), in which the rate-limiting reaction is catalyzed by CTP: phosphocholine cytidylyltransferase (CT) (5Vance D.E. Pelech S. Trends Biochem. Sci. 1984; 9: 17-20Abstract Full Text PDF Scopus (101) Google Scholar). Three CT isoforms, encoded by two genes, have been identified in rodents. CTα is encoded by the Pcyt1a gene, whereas CTβ2 and CTβ3 are derived from the Pcyt1b gene (6Lykidis A. Murti K.G. Jackowski S. J. Biol. Chem. 1998; 273: 14022-14029Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar, 7Lykidis A. Baburina I. Jackowksi S. J. Biol. Chem. 1999; 274: 26992-27001Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar). CTα and CTβ2 share considerable sequence identity, but CTα contains a nuclear localization signal (8Wang Y. Sweitzer T.D. Weinhold P.A. Kent C. J. Biol. Chem. 1993; 268: 5899-5904Abstract Full Text PDF PubMed Google Scholar), whereas CTβ2 does not (7Lykidis A. Baburina I. Jackowksi S. J. Biol. Chem. 1999; 274: 26992-27001Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar). Immunofluorescence studies have found that CTα is primarily located in the nucleus and that CTβ2 resides in the cytosol and on the endoplasmic reticulum (9Ridsdale R. Tseu I. Wang J. Post M. J. Biol. Chem. 2001; 276: 49148-49155Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar). The subcellular localization of CTβ3 has not yet been reported. Although CTα is expressed in all tissues, CTβ2 and CTβ3 mRNAs are predominantly expressed in the brain (6Lykidis A. Murti K.G. Jackowski S. J. Biol. Chem. 1998; 273: 14022-14029Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar). In neurons, PC is synthesized not only in cell bodies but also in distal axons (4Vance J.E. Pan D. Campenot R.B. Bussiere M. Vance D.E. J. Neurochem. 1994; 62: 329-337Crossref PubMed Scopus (94) Google Scholar, 10Strosznajder J. Radominska-Pyrek A. Horrocks L.A. Biochim. Biophys. Acta. 1979; 574: 48-56Crossref PubMed Scopus (24) Google Scholar, 11Tanaka T. Yamaguchi H. Kishimoto Y. Gould R.M. Biochim. Biophys. Acta. 1987; 922: 85-94Crossref PubMed Scopus (13) Google Scholar, 12Vance J.E. Pan D. Vance D.E. Campenot R.B. J. Cell Biol. 1991; 115: 1061-1068Crossref PubMed Scopus Google Scholar). neurite outgrowth of PC12 cells and cells, CTβ2 expression and CT are increased, whereas CTα expression is a CTβ2 expression and neurite outgrowth J.M. Waite K.A. Campenot R.B. Vance J.E. Vance D.E. J. Biol. Chem. 2003; 278: 44988-44994Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar). are by to the cell neurites from the cell neurites from primary The sprouting of primary neurites and are processes that are A. J. Full Text Full Text PDF PubMed Scopus Google Scholar). neuronal NGF which Akt T. I. C. A. K. A. J. Cell Sci. PubMed Google Scholar). Neurite and branching are promoted in of neurons by activation of whereas in neurons activation of Akt neurite elongation and branching K. M. K. J. PubMed Google Scholar). In PC12 cells, Akt activation neurite branching M. K. Y. 2003; PubMed Scopus Google Scholar). the of these that neurons CTβ2 in axons to a of PC for neurite extension, branching. We show that CTβ2 is abundant in PC12 cells and in distal axons of primary of RNA silencing of CTβ2 in PC12 cells reduced the of primary neurites and markedly reduced the of but increased the length of individual of neurite branching in PC12 cells, a that is by inhibition of was in CTβ2-deficient cells. These into the of CTβ2 and PC biosynthesis in neurite sprouting and Cell pheochromocytoma cells (PC12) were from the Cell were in and in a differentiation and cells were on a of The cells were and and NGF and cells were for to of and neurons from the of were previously R. Biol. PubMed Scopus Google Scholar). the were and and into the of all NGF NGF was from the cell bodies and The distal axons NGF the ganglion cells were from and in previously H. Campenot R.B. Vance D.E. Vance J.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). distal axons of sympathetic neurons, and distal axons of retinal ganglion cells were from H. Campenot R.B. Vance D.E. Vance J.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, E. Bussiere M. Vance D.E. Campenot R.B. Vance J.E. J. Biol. Chem. 2001; 276: Full Text Full Text PDF PubMed Scopus Google Scholar). that CTβ2 were the membrane of rat CT and were a from R. CTβ2 were a from S. Jackowski The was a to of CTβ2 (7Lykidis A. Baburina I. Jackowksi S. J. Biol. Chem. 1999; 274: 26992-27001Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar). The were from and the and were from Cell The Cdk5 was from of PC12 and of Neurite and cells were a of for which the was to were of RNA cells were a expression green fluorescent protein and rat PC12 cells were of and the silencing a CTβ2 cells were a a hemagglutinin CTβ2 and The cells were in the of to the the and were in a to for to of which were to PC12 cells. the cells were NGF to differentiation and neurite and cells were by that been and were identified by neurite were to be and all neurites and were of were and of PC12 cells of sympathetic neurons and retinal ganglion cells were and into of and a inhibitor Cell were for and were for of on a of was and the were for CTβ2 were and were from the and and for were by on and to was used to protein in of the The were blocked for in and and were for and to for was In of CT cells from two were in of and of and The cells were for Cell were for to and cells. of the were used for of CT and CT was in the of by the of to S. Vance D. J. Biol. Chem. Full Text PDF PubMed Google Scholar). of PC12 cells were control the was to that cells were for were the amount of protein was and in PC was In of cells were NGF for which the cells were for LY294002 for roscovitine an of in the of were and into The cell were for which were on a a of protein were and the was for an CTβ2 were CTβ2 was from the by for in were by on The was and to a for to of CT protein was a In cells were into of CTβ2 was was Cdk5 was protein were for CTβ2 protein was from the and and for The CTβ2 protein was to in the of of and for The reaction was by for in the of were by on The were and to a for to and were for to and cells. were and by on were by of the to and identified by The were from the and of were by J. Full Text PDF PubMed Google Scholar). RNA for CTβ2 mRNA was a sequence and synthesized the of of The sequence showed to in the was the to mRNA in The was into and the was of the was by and of CTβ2 the of CTβ2 was from a from PC12 cell mRNA the and The was into and used a for the of an to the of the The sequence encoded the The was into the expression and of protein was by of from of cells and were the protein a LY294002 and roscovitine were from and in CTβ2 in of and of that NGF increases the expression of CTβ2 in PC12 cells J.M. Waite K.A. Campenot R.B. Vance J.E. Vance D.E. J. Biol. Chem. 2003; 278: 44988-44994Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar), that the subcellular localization of CT neurons into to PC biosynthesis and neurite Our has previously that PC biosynthetic enzyme are in distal axons of rat sympathetic neurons (4Vance J.E. Pan D. Campenot R.B. Bussiere M. Vance D.E. J. Neurochem. 1994; 62: 329-337Crossref PubMed Scopus (94) Google Scholar). The that in cell CTα is predominantly whereas is that is a CT isoform in We CT from PC12 cells, rat sympathetic neurons, and retinal ganglion cells an the membrane of rat We that CTβ2 was by the by the from retinal ganglion cells on these and the of CTβ2 identified the in of the in the of primary identified the in the of the CTβ2 was also in PC12 cells and rat sympathetic neurons not axons CT from distal axons of of sympathetic neurons and retinal ganglion cells. In cell bodies and axons are from distal axons by a and a R. Biol. PubMed Scopus Google Scholar). distal axons be from cell in of that CTβ2 is abundant in distal axons and cell axons of sympathetic neurons and also in distal axons of retinal ganglion cells. These experiments that CTβ2 is in PC12 cells in distal axons of rat sympathetic neurons and rat retinal ganglion cells. CTβ2 of and CTβ2 is in axons and the amount of but not is increased during neurite outgrowth J.M. Waite K.A. Campenot R.B. Vance J.E. Vance D.E. J. Biol. Chem. 2003; 278: 44988-44994Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar), that CTβ2 neurite We that of CTβ2 expression in PC12 cells neurite used a RNA silencing to expression of CTβ2 in PC12 cells. PC12 cells were a expression and a small interfering RNA to CTβ2 mRNA a a The cells were NGF to differentiation and neurite We that was to the of cells that expressed in of In the amount of CTβ2 by was reduced that in control cells of that protein in was not We also the in vitro of CT in the of CTα and In cells, CT was whereas CT of control cells was protein reduced CT in CTβ2-silenced cells was However, CT the of CTα isoform of and and RNA of CTβ2 was in only of the cells, is that CTβ2 was reduced in the cells. the of of total CT in cells, the of into PC in PC12 cells a was not significantly reduced of protein for control and of protein for of CTβ2 expression the of PC12 cells, the cells were and and the of cells and the were cells were identified by the of of NGF the of neurites neurites cell was markedly in CTβ2-deficient cells in cells a in control cells of NGF in the of neurites the of neurite and neurite length cells and control cells were and and the neurites of cells in a of to the and in numbers of primary neurites and the total of primary neurites and cell in control and CTβ2-deficient cells a of of NGF control cells neurites cell CTβ2-deficient cells NGF control cells primary neurites and of NGF control cells In CTβ2-deficient cells only increased the of neurites and a of to CTβ2-deficient cells the neurites of control cells primary neurites and are neurite that are by A. A. Trends Full Text Full Text PDF PubMed Scopus Google Scholar), a decrease in the amount of CTβ2 of these neurite of NGF the of neurite sprouting was significantly in CTβ2-deficient cells in control cells The in the of primary neurites was of differentiation CTβ2-deficient cells control cells and of NGF CTβ2 neurite sprouting and branching. CTβ2 for Neurite a primary neurite has from the cell the neurite to neurite for CTβ2-deficient PC12 cells neurites primary neurites and control cells and the of primary neurites and to not CTβ2 is for neurite In control cells, neurite length primary neurites and not increase and and a neurite a length of and elongation of the primary neurite was However, of primary neurites of CTβ2-deficient cells the of NGF by neurites of CTβ2-deficient cells were of control cells In to the increase in length and of neurites of cells also from neurites of control cells. neurites of control cells, neurites of CTβ2-deficient cells in of to the of the neurite for silencing of CTβ2 expression in PC12 cells the of neurites is that the and of PC were the total length of all neurites the of the length of all primary neurites and in control cells and CTβ2-deficient cells. and of NGF the total length of neurites was not control and CTβ2-deficient cells and the total length of all neurites cell the total amount of membrane were the in control and cells, that in the amount of CTβ2 does not neurite of CTβ2 in PC12 Neurite of CTβ2 expression in PC12 cells significantly total neurite not of CTβ2 increased neurite sprouting and We a CTβ2 and into a expression of protein in PC12 cells was by of of cells that a protein to the of was expressed in cells. Accordingly, CT in of cells was significantly in control cells protein CTβ2 neurite PC12 cells a to and cells that expressed of NGF the cells were by and numbers of primary neurites and were cells whereas control cells Although is not is a an increased of neurites in cells. expression of CTβ2 not significantly increase the of primary neurites in control cells in a increased of of CTβ2 not significantly increase the of in control cells in cells whereas of CTβ2 expression reduced the of primary neurites and of CTβ2 not significantly increase the of primary neurites silencing of CTβ2 expression not total neurite length that the of membrane in PC12 cells be by in CTβ2 the of of cell of and was not significantly by of CTβ2 in cells in which CTβ2 expression was reduced cells the total amount of in PC12 cells was not by a decrease an increase in the of these that CTβ2 is for neurite branching and sprouting but not for neurite CTβ2 for of Neurite the by which of CTβ2 neurite sprouting and branching. of Akt has been to neurite branching in PC12 cells, of the cells an inhibitor of Akt activation and promoted neurite branching M. K. Y. 2003; PubMed Scopus Google Scholar). that CTβ2 a in neurite outgrowth and that CTβ2 be a of the the of LY294002 on neurite outgrowth and in control PC12 cells and in PC12 cells in which CTβ2 expression been of that LY294002 reduced the phosphorylation of Akt a M. K. Y. 2003; PubMed Scopus Google Scholar), PC12 cells LY294002 neurites cells for cells for control cells In expression of CTβ2 in cells blocked the increase in the total of neurites that was in control cells LY294002 CTβ2-deficient cells in the of LY294002 and cells We also the of primary neurites and to LY294002 of these neurite In control cells, LY294002 increased the of primary by and increased the of by to In CTβ2-deficient cells, on the LY294002 not increase the of primary neurites CTβ2-deficient cells primary whereas CTβ2-deficient cells primary CTβ2-deficient cells control cells LY294002 increased the of by to the of in control cells. these the that is for neurite branching. of CT isoform to CT in PC12 cells. We not LY294002 the phosphorylation of the not neurite sprouting and only increased branching in CTβ2-deficient cells, that CTβ2 be a of the CTβ2 is phosphorylated in (7Lykidis A. Baburina I. Jackowksi S. J. Biol. Chem. 1999; 274: 26992-27001Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar). However, studies on the and that on CTβ2 have not been reported. In cells, and growth factor CT phosphorylation M. T. 1994; PubMed Scopus Google Scholar), and cells CTα and mRNAs (7Lykidis A. Baburina I. Jackowksi S. J. Biol. Chem. 1999; 274: 26992-27001Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar). is that CTβ2 is phosphorylated in response to growth the sequence of identified a Akt phosphorylation the of CTβ2 was a for phosphorylation by differentiated PC12 cells LY294002 an of for The cells were for and CTβ2 was and by in of PC12 cells LY294002 reduced the phosphorylation of Akt but not significantly the of CTβ2 in PC12 cells, CTβ2 is to be by Akt for phosphorylation of CTβ2 is Cdk5 J. S. Trends Cell Biol. 1999; 9: Full Text Full Text PDF PubMed Scopus Google Scholar). a of and that the cell Cdk5 has sequence to and is the isoform that is highly in brain Cell 2001; Google Scholar). Cdk5 is for growth M. H. PubMed Scopus Google and is during of nerve axons U. S. PubMed Scopus Google Scholar). CTβ2 has a Cdk5 phosphorylation We not CTβ2 was phosphorylated by CTβ2 was from of PC12 cells and used a for Cdk5 phosphorylation in an in vitro We used a a Cdk5 phosphorylation and is not known to be phosphorylated by in CTβ2 was phosphorylated in vitro by whereas was Cdk5 CTβ2 in Cdk5 also phosphorylated CTβ2 in cells. CTβ2 were phosphorylated by of PC12 cells a be to of PC12 cells were and roscovitine for to of the cells CTβ2 was from cell and the of into CTβ2 was that was into CTβ2 in PC12 cells roscovitine in cells. These that CTβ2 is a for In roscovitine of PC12 cells markedly reduced neurite branching suggesting a reduced phosphorylation and of CTβ2 and inhibition of neurite branching. the of roscovitine used for these experiments for PC12 cell was for for the of cells was the for control cells for cells We the of an isoform of CT rate-limiting enzyme in PC in neurite sprouting, extension, and branching of PC12 cells. We show that CTβ2 is abundant in PC12 cells, in axons of rat sympathetic neurons and rat retinal ganglion cells. the amount of CTβ2 protein was reduced in PC12 cells by RNA neurite the total of neurites and the of primary neurites cell were markedly whereas the total length of neurites was unchanged. These that CTβ2 a in neurite sprouting and branching but not in neurite Our studies also that CTβ2 is for the of neurite outgrowth that the Akt pathway is We show that CTβ2 is phosphorylated by Cdk5 and that inhibition of Cdk5 by roscovitine neurite a phosphorylation and of CTβ2 and neurite branching. CTβ2 in and Neurite and are not synthesized in cell bodies of neurons J.E. Pan D. Vance D.E. Campenot R.B. J. Cell Biol. 1991; 115: 1061-1068Crossref PubMed Scopus Google Scholar), and of the pathway for PC biosynthesis have been in distal axons of rat sympathetic neurons (4Vance J.E. Pan D. Campenot R.B. Bussiere M. Vance D.E. J. Neurochem. 1994; 62: 329-337Crossref PubMed Scopus (94) Google and in rat brain J. Radominska-Pyrek A. Horrocks L.A. Biochim. Biophys. Acta. 1979; 574: 48-56Crossref PubMed Scopus (24) Google Scholar). of PC in is axons E. Vance D.E. Campenot R.B. Vance J.E. J. Cell Biol. PubMed Scopus Google Scholar). distal but not cell of sympathetic neurons are of PC growth is significantly E. Vance D.E. Campenot R.B. Vance J.E. J. Cell Biol. PubMed Scopus Google Scholar). The biosynthesis of and has also been in axons of rat sympathetic neurons (4Vance J.E. Pan D. Campenot R.B. Bussiere M. Vance D.E. J. Neurochem. 1994; 62: 329-337Crossref PubMed Scopus (94) Google Scholar). the of a has been in axons of neurons M. J. 2001; PubMed Google Scholar). not all lipid are in distal biosynthesis to be to cell axons (4Vance J.E. Pan D. Campenot R.B. Bussiere M. Vance D.E. J. Neurochem. 1994; 62: 329-337Crossref PubMed Scopus (94) Google Scholar). The expression of CTβ2 mRNA in the is in the brain S. J.E. Wang J. K. Biol. PubMed Scopus Google Scholar). However, of the cells in the brain are cells, not neurons in J.M. J. Full Text Full Text PDF PubMed Scopus Google Scholar), not the of expression of CTβ2 in neurons of cells in the brain. We show that CTβ2 is abundant in PC12 cells and in distal axons of sympathetic neurons and retinal ganglion cells on these that of PC CTβ2 be for of neurite sprouting, CTβ2 expression in PC12 cells. of CTβ2 expression neurite and reduced neurite sprouting and In the total length of all neurites was not an of not CTβ2 neurite sprouting and expressed CTβ2 in PC12 cells. The amount of CTβ2 protein and CT were increased, but the of neurites was not significantly the amount of CTβ2 and CTα in PC12 cells PC for neurite sprouting and branching CTβ2 is not the for these have identified in PC12 cells, the and the that are for branching of neurites H. H. Y. K. M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). and in PC12 cells CTβ2 for Neurite a neurite and K. J. PubMed Scopus Google Scholar). In CTβ2-deficient PC12 cells, a decrease in neurite branching but an increase in the length of individual primary of in neurons has that growth for to the of K. J. 1998; PubMed Google Scholar). and the the and into the neurite in K. J. PubMed Scopus Google Scholar). an neurite is to for and for growth of the neurites results in of has also been in PC12 cells that a known to neurite growth and PC12 cells Akt significantly neurites control cells that but the neurites in control cells that Akt M. K. Y. 2003; PubMed Scopus Google Scholar). of Akt to neurite branching. LY294002 is a inhibitor that the activation of Akt M. K. Y. 2003; PubMed Scopus Google Scholar). of control PC12 cells LY294002 increased the of neurites primary neurites and However, in CTβ2-deficient PC12 cells, LY294002 to increase the of primary neurites CTβ2 is for the of sprouting by inhibition of the CTβ2 contains a Akt phosphorylation We not CTβ2 is phosphorylated by Akt in cells. LY294002 of PC12 cells not the of CTβ2 suggesting that CTβ2 is not by phosphorylation Akt. NGF is known to in neurons PubMed Scopus Google Scholar). Cdk5 and are abundant in the brain and are the by NGF T. T. S. E. Cell Biol. 2001; PubMed Scopus Google these have been in growth and M. H. PubMed Scopus Google Scholar, U. S. PubMed Scopus Google Scholar), and Cdk5 to be in CTβ2 contains a Cdk5 phosphorylation that Cdk5 that Cdk5 CTβ2 in vitro and in cells In of PC12 cells a markedly CTβ2 phosphorylation and neurite branching in cells. CTβ2 and Cdk5 H. S. K. PubMed Scopus Google are of that Cdk5 and branching. In axons branching J. Wang Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). inhibition of Cdk5 roscovitine elongation H. S. K. PubMed Scopus Google Scholar). that Cdk5 is CTβ2 is phosphorylated and and neurite outgrowth and branching are and Neurite have identified the first lipid biosynthetic enzyme that facilitates neurite sprouting and C. A. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google that of a enzyme, significantly increases neurite in PC12 cells. However, the numbers of neurites and were unchanged. is that CTβ2 a synthesized of PC in axons axons of neurons were the the cell lipid for the membrane and for the growth U. R. Full Text Full Text PDF PubMed Scopus Google Scholar). In to membrane for neurite sprouting and CTβ2 PC that has been in PC J. J. Neurochem. 1991; PubMed Scopus Google and is in PC12 cells R.J. J. Neurochem. PubMed Scopus Google Scholar). Neurite outgrowth in PC12 cells activation of the H. T. M. H. T. T. K. Y. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). In (2Araki W. Wurtman R.J. Proc. Natl. Acad. Sci. U. S. A. 1997; 94: 11946-11950Crossref PubMed Scopus (75) Google Scholar), that inhibition of the protein pathway by CT a for protein in activation of CTβ2 the of PC that has been by D. in CTβ2 PC that phosphocholine for be in distal axons of sympathetic neurons (4Vance J.E. Pan D. Campenot R.B. Bussiere M. Vance D.E. J. Neurochem. 1994; 62: 329-337Crossref PubMed Scopus (94) Google and is a of in C. J. 1999; PubMed Scopus Google Scholar). a for CTβ2 in neurite outgrowth branching that is of in PC The CDP-choline pathway for PC biosynthesis in rat sympathetic neurons (5Vance D.E. Pelech S. Trends Biochem. Sci. 1984; 9: 17-20Abstract Full Text PDF Scopus (101) Google Scholar), by CT In PC12 cells, PC biosynthesis has also been to be by the of and by the of the enzyme that the of the CDP-choline pathway (2Araki W. Wurtman R.J. Proc. Natl. Acad. Sci. U. S. A. 1997; 94: 11946-11950Crossref PubMed Scopus (75) Google Scholar). and of PC biosynthesis in PC12 cells Wurtman R.J. J. Neurochem. PubMed Scopus Google and rat brain Wurtman R.J. J. Neurochem. PubMed Scopus Google Scholar). of PC12 cells increased CDP-choline and neurite outgrowth and in a R. Wurtman R.J. PubMed Scopus Google Scholar). of neurite outgrowth was in to an increased amount of CDP-choline R. Wurtman R.J. PubMed Scopus Google Scholar). that the amount of CTβ2 protein and PC biosynthesis during PC12 cell In that CTβ2 facilitates neurite outgrowth and branching. CTβ2 to be in neurite and is abundant in the that a of CTβ2 in in and We and for and for of rat retinal ganglion cells.

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