Scyl1, Mutated in a Recessive Form of Spinocerebellar Neurodegeneration, Regulates COPI-mediated Retrograde Traffic

Scy1-like 1 (Scyl1), a member of the Scy1-like family of catalytically inactive protein kinases, was recently identified as the gene product altered in muscle-deficient mice, which suffer from motor neuron degeneration and cerebellar atrophy. To determine the function of Scyl1, we have now used a mass spectrometry-based screen to search for Scyl1-binding partners and identified components of coatomer I (COPI) coats. The interaction was confirmed in pull-down assays, and Scyl1 co-immunoprecipitates with βCOP from brain lysates. Interestingly, and unique for a non-transmembrane domain protein, Scyl1 binds COPI coats using a C-terminal RKLD-COO- sequence, similar to the KKXX-COO- COPI-binding motif found in transmembrane endoplasmic reticulum (ER) proteins. Scyl1 co-localizes with βCOP and is localized, in an Arf1-independent manner, to the ER-Golgi intermediate compartment and the cis-Golgi, sites of COPI-mediated membrane budding. The localization and binding properties of Scyl1 strongly suggest a function in COPI transport, and inhibitory RNA-mediated knock down of the protein disrupts COPI-mediated retrograde traffic of the KDEL receptor to the ER without affecting anterograde traffic from the ER. Our data demonstrate a function for Scyl1 as an accessory factor in COPI trafficking and suggest for the first time that alterations in the COPI pathway result in neurodegenerative disease. Scy1-like 1 (Scyl1), a member of the Scy1-like family of catalytically inactive protein kinases, was recently identified as the gene product altered in muscle-deficient mice, which suffer from motor neuron degeneration and cerebellar atrophy. To determine the function of Scyl1, we have now used a mass spectrometry-based screen to search for Scyl1-binding partners and identified components of coatomer I (COPI) coats. The interaction was confirmed in pull-down assays, and Scyl1 co-immunoprecipitates with βCOP from brain lysates. Interestingly, and unique for a non-transmembrane domain protein, Scyl1 binds COPI coats using a C-terminal RKLD-COO- sequence, similar to the KKXX-COO- COPI-binding motif found in transmembrane endoplasmic reticulum (ER) proteins. Scyl1 co-localizes with βCOP and is localized, in an Arf1-independent manner, to the ER-Golgi intermediate compartment and the cis-Golgi, sites of COPI-mediated membrane budding. The localization and binding properties of Scyl1 strongly suggest a function in COPI transport, and inhibitory RNA-mediated knock down of the protein disrupts COPI-mediated retrograde traffic of the KDEL receptor to the ER without affecting anterograde traffic from the ER. Our data demonstrate a function for Scyl1 as an accessory factor in COPI trafficking and suggest for the first time that alterations in the COPI pathway result in neurodegenerative disease. The murine autosomal recessive neurodegenerative disease model “muscle-deficient” (mdf) displays clinical and histological features indicative of a progressive motor neuropathy (1Blot S. Poirier C. Dreyfus P.A. J. Neuropathol. Exp. Neurol. 1995; 54: 812-825Crossref PubMed Scopus (27) Google Scholar). Homozygotes develop a posterior waddle at 4-8 weeks of age followed by hind limb paralysis and forelimb weakness (1Blot S. Poirier C. Dreyfus P.A. J. Neuropathol. Exp. Neurol. 1995; 54: 812-825Crossref PubMed Scopus (27) Google Scholar). Skeletal muscles exhibit a neurogenic atrophy, and there is progressive neurodegeneration of lower motor neurons (1Blot S. Poirier C. Dreyfus P.A. J. Neuropathol. Exp. Neurol. 1995; 54: 812-825Crossref PubMed Scopus (27) Google Scholar, 2Cabanes C. Bonilla S. Tabares L. Martinez S. Neurobiol. Dis. 2007; 26: 408-418Crossref PubMed Scopus (53) Google Scholar). Among the murine neuromuscular atrophies, the motor neuron degeneration in mdf is most similar to that seen in wobbler (1Blot S. Poirier C. Dreyfus P.A. J. Neuropathol. Exp. Neurol. 1995; 54: 812-825Crossref PubMed Scopus (27) Google Scholar). Interestingly, mdf also suffers from symptoms indicative of cerebellar involvement including gait ataxia, abnormal hind limb posture, and tremor (3Schmidt W.M. Kraus C. Hoger H. Hochmeister S. Oberndorfer F. Branka M. Bingemann S. Lassmann H. Muller M. Macedo-Souza L.I. Vainzof M. Zatz M. Reis A. Bittner R.E. EMBO Rep. 2007; 8: 691-697Crossref PubMed Scopus (55) Google Scholar). Therefore, mdf appears to be linked to both neuromuscular atrophy and spinocerebellar ataxia and is thus an animal model for neuromuscular disease with cerebellar involvement in humans. Most recently, null mutations in the Scy1-like 1 (Scyl1) gene were determined to be responsible for the pathology seen in the mdf mouse (3Schmidt W.M. Kraus C. Hoger H. Hochmeister S. Oberndorfer F. Branka M. Bingemann S. Lassmann H. Muller M. Macedo-Souza L.I. Vainzof M. Zatz M. Reis A. Bittner R.E. EMBO Rep. 2007; 8: 691-697Crossref PubMed Scopus (55) Google Scholar). Scyl1 was initially identified as a ubiquitously expressed member of the Scy1-like family of protein kinases (4Liu S.C. Lane W.S. Lienhard G.E. Biochim. Biophys. Acta. 2000; 1517: 148-152Crossref PubMed Scopus (17) Google Scholar) and is a distant homologue of Scy1-like 2/CVAK104 (coated vesicle-associated kinase of 104 kDa), which is involved in the trafficking of clathrin-coated vesicles (CCVs) 3The abbreviations used are:CCVclathrin-coated vesicleCOPIcoatomer IAP-2adaptor protein-2KDELRKDEL receptorERendoplasmic reticulumERGICER/Golgi intermediate compartmentKDknockdownsiRNAsmall inhibitory RNAmiRNAmicroRNATGNtrans-Golgi networkBFAbrefeldin AVSVGvesicular stomatitis virus G proteinGFPgreen fluorescent proteinEmGFPemerald GFPYFPyellow fluorescent proteinRFPred fluorescent proteinmRFPmonomeric RFPFTCDformiminotransferase cyclodeaminaseGSTglutathione S-transferaseMSmass spectrometry. (5Wasiak S. Legendre-Guillemin V. Puertollano R. Blondeau F. Girard M. de Heuvel E. Boismenu D. Bell A.W. Bonifacino J.S. McPherson P.S. J. Cell Biol. 2002; 158: 855-862Crossref PubMed Scopus (167) Google Scholar, 6Conner S.D. Schmid S.L. J. Biol. Chem. 2005; 280: 21539-21544Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar, 7Düwel M. Ungewickell E.J. Mol. Biol. Cell. 2006; 17: 4513-4525Crossref PubMed Google Scholar). Scy1-like kinases are thought to be kinase-inactive as they lack several highly conserved residues essential for catalytic activity (8Hanks S.K. Quinn A.M. Hunter T. Science. 1988; 241: 42-52Crossref PubMed Scopus (3826) Google Scholar, 9Manning G. Plowman G.D. Hunter T. Sudarsanam S. Trends Biochem. Sci. 2002; 27: 514-520Abstract Full Text Full Text PDF PubMed Scopus (742) Google Scholar). Scyl1 was indirectly implicated in clathrin-mediated endocytosis when it was identified as an in vitro binding partner for the α- and β2-ear domains of the clathrin adaptor protein-2 (AP-2) (in this study, Scyl1 was referred to as CVAK90) (10Schmid E.M. Ford M.G. Burtey A. Praefcke G.J. Peak-Chew S.Y. Mills I.G. Benmerah A. McMahon H.T. PLoS Biol. 2006; 4: PubMed Scopus Google and when it was to be of that the of stomatitis virus in a inhibitory screen of the L. E. H. M. E. M. 2005; PubMed Scopus Google Scholar). of Scyl1, as was found to to and was thus to be involved in M. H. 2002; PubMed Scopus Google Scholar). clathrin-coated coatomer I adaptor protein-2 KDEL receptor endoplasmic reticulum intermediate compartment inhibitory stomatitis virus G protein fluorescent protein fluorescent protein fluorescent protein mass spectrometry. we a and of Scyl1 in an to the in which the protein Our data that Scyl1 binds to and co-localizes with the membrane trafficking coatomer I (COPI) and that this interaction is a to the KKXX-COO- motif that transmembrane protein with COPI coats T. M. P.A. Cell. Full Text PDF PubMed Scopus Google Scholar, F. Science. PubMed Scopus Google Scholar, M. J. S. A. T. J. Cell Biol. PubMed Scopus Google Scholar). Our data the localization of Scyl1 to the at the endoplasmic reticulum intermediate compartment and the cis-Golgi, both of which are sites COPI is to function in to ER retrograde RNA-mediated of Scyl1 to a in trafficking of the KDEL receptor from the to the ER. Scyl1 in COPI-mediated a this pathway and neurodegenerative and the C-terminal most of mouse Scyl1 for was a from Lienhard (4Liu S.C. Lane W.S. Lienhard G.E. Biochim. Biophys. Acta. 2000; 1517: 148-152Crossref PubMed Scopus (17) Google Scholar). the of adaptor protein 1 the of adaptor protein and the were from the and receptor were from and and were from and for was from used for was a from M. J. S. A. T. J. Cell Biol. PubMed Scopus Google and βCOP used for was from M. J. S. A. T. J. Cell Biol. PubMed Scopus Google Scholar) was from was by βCOP for and was from 1 was J. C. McPherson P.S. EMBO J. PubMed Scopus Google Scholar). the of Scyl1 and were with a by from was from the were as in the and pull-down assays, were in and and at for the was and was to at the were at for the was to 1 and was to of 1 were for at with to were with with and and by with were and by mass as F. S. Girard M. A. Legendre-Guillemin V. L. Boismenu D. R.E. Bell A.W. McPherson P.S. Sci. S. A. PubMed Scopus Google Scholar) were for of the C-terminal of Scyl1 were to and were with at of to protein to the of the and of the as assays, as were with to protein protein and the were as for the pull-down is in the RNA-mediated of were used to Scyl1 in and were from and of were at in without and with a to a of using the to the were at at with was the and were an at were for of a were in and and at at for and the was for protein were and to Scyl1 was using a an to Scyl1 The the were with partners and the in which the for was with were with as was with and anterograde trafficking were as J. PubMed Scopus Google Scholar, J. J. J. Cell Biol. PubMed Scopus Google Scholar). the first of the were to the of and an they were to to protein were to the of and at time they were and for a of was of and retrograde were as J. J. D. J. J. Cell Biol. PubMed Scopus Google Scholar, J.S. S.Y. S. H. L. M. D. A. EMBO J. 2005; PubMed Scopus Google Scholar). at of the were at the of for 1 this of the were and for The were at the of for 1 at which they were and for retrograde trafficking were in with of a a in the J. J. D. J. J. Cell Biol. PubMed Scopus Google Scholar). The a of of were with were and for were at the of for 1 at which they were and for Scyl1 with COPI is of an domain and a C-terminal factor and a domain To the function of Scyl1, we for partners using pull-down from brain with Scyl1 the C-terminal were by followed by and is for both and lower to a Scyl1-binding partner was at with both of the to to with of the is member of the COPI which also and F. C. Cell Biol. PubMed Scopus Google Scholar, M. 2000; PubMed Google Scholar, T. Mol. Cell. Biol. 2000; PubMed Scopus Google Scholar). was seen at with the C-terminal of this the α- and of the which is involved in as as βCOP and The of α- and is with the of Scyl1 in using the domains of α- and (10Schmid E.M. Ford M.G. Burtey A. Praefcke G.J. Peak-Chew S.Y. Mills I.G. Benmerah A. McMahon H.T. PLoS Biol. 2006; 4: PubMed Scopus Google Scholar). The of and that Scyl1 binds to components of COPI coats. was by βCOP of Scyl1 which that the interaction with both the protein and the C-terminal of βCOP from brain to a of Scyl1 and βCOP in with Scyl1 the we of Scyl1 and the and data Scyl1 as a COPI-binding Scyl1 COPI a to determine the binding Scyl1 for COPI coats. 1 membrane a is at the and is an ER M. J. S. A. T. J. Cell Biol. PubMed Scopus Google Scholar). KKXX-COO- the COPI to ER that have from the ER COPI vesicles for retrograde T. M. P.A. Cell. Full Text PDF PubMed Scopus Google Scholar, F. Science. PubMed Scopus Google Scholar). COPI-binding are found in the family of which the ER and the M. J. S. A. T. J. Cell Biol. PubMed Scopus Google Scholar). KKXX-COO- have to C. Sci. S. A. PubMed Scopus Google Scholar) the domains at the of and A. G. M. R. EMBO J. 2000; PubMed Scopus Google Scholar, A. D. M. R. Mol. Biol. Cell. PubMed Scopus Google Scholar). a that KKXX-COO- from ER and to and that this J. M. J. F. Mol. Cell. Biol. 2006; 26: PubMed Scopus Google Scholar). Interestingly, the Scyl1 a that with the RKLD-COO- of the of Scyl1 binding to COPI as with an βCOP of to to a similar in binding The binding seen with is of the domain of Scyl1 and Scyl1 a similar to the found in and for binding to COPI with a COPI-binding in the To the COPI binding properties of the RKLD-COO- with a KKXX-COO- we a protein the of with which was to COPI coats M. J. S. A. T. J. Cell Biol. PubMed Scopus Google Scholar). binds as by βCOP there is binding to there is Scyl1 protein in the To this we binding a of protein from to for and for βCOP binding to Scyl1 at protein with binding at binding to and the binding is Scyl1 appears to have for COPI coats. To the to the sites COPI we in which was with brain in the of of a the C-terminal most residues of Scyl1 including the C-terminal most residues of including an and to binding of to the of S. Legendre-Guillemin V. McPherson P.S. J. 2006; 26: PubMed Scopus Google Scholar). of COPI coats was by βCOP the Scyl1 binding of to COPI the the both the and the Scyl1 binding of COPI coats to the for data is that the RKLD-COO- of Scyl1 binds to a COPI coats when with the of Scyl1 binding is of and the are the Scyl1 is to binding of to unique in COPI coats. is also that Scyl1 binding sites COPI of that is unique from that of and a that is to that of KKXX-COO- be to and to determine the binding and COPI coats. Scyl1 with the localization of Scyl1 by in and Scyl1 in and that were in a in is in the and the of Scyl1 with βCOP of data strongly that the is and to Scyl1 co-localizes with βCOP at both and in the are seen for a Scyl1 and data as determined by Scyl1 to a and in Scyl1 in when with a and both to a in with the Scyl1 The of both the and the of Scyl1 is in in which with were to the used to Scyl1 in this is the as that used by (3Schmidt W.M. Kraus C. Hoger H. Hochmeister S. Oberndorfer F. Branka M. Bingemann S. Lassmann H. Muller M. Macedo-Souza L.I. Vainzof M. Zatz M. Reis A. Bittner R.E. EMBO Rep. 2007; 8: 691-697Crossref PubMed Scopus (55) Google Scholar) in which mdf from of Scyl1 Scyl1 also binds to α- and in pull-down (10Schmid E.M. Ford M.G. Burtey A. Praefcke G.J. Peak-Chew S.Y. Mills I.G. Benmerah A. McMahon H.T. PLoS Biol. 2006; 4: PubMed Scopus Google L. L. J. T. S. J. F. and S. it with the Scyl1 is and that the protein is to with binding to COPI co-localizes with βCOP at the with were for to βCOP and The of of is in the The is the of and the in the is at to the The to protein of from with were for with the proteins. with were for with the Scyl1 were for the and the were for from the of with were the and for with the Scyl1 The of Scyl1 The of Scyl1 to the coats membrane the the of Scyl1 to of the To this we first with protein of the and and the Scyl1 in with also as a E. J. Cell Biol. PubMed Scopus Google Scholar, C. E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). is seen in was to the of Scyl1, and of with the Scyl1 was with a of the of Scyl1 was seen with The of is to the is also found that there is Scyl1 at was of Scyl1 with the protein data suggest that the of Scyl1 is to the and is at the co-localizes with the with were for to Scyl1 The of is in the The is at The lower of is at to in the with to To the localization of Scyl1 and to determine the localization of the protein the we the of is a that the to by the anterograde of from ER in the of E. J. Cell Biol. PubMed Scopus Google Scholar, J. S. T. T. J. Cell Biol. PubMed Scopus Google Scholar, S. J. J. Cell Biol. PubMed Scopus Google Scholar). are in the localization of a protein the of the of a of with Scyl1 to it with and a C. R. T. G. J. Cell Biol. 1995; PubMed Scopus Google Scholar) Scyl1 with in the localization of to the and the using of and a that the of an protein to the of and in S.Y. A. J. 2007; PubMed Scopus (29) Google Scholar). this the of the protein is a in which and to the of the is found in S.Y. A. J. 2007; PubMed Scopus (29) Google Scholar). Scyl1 a of with an localization for the of the protein to a which is used as a in a of with S.Y. A. J. 2007; PubMed Scopus (29) Google Scholar). data strongly that the of Scyl1 is to Interestingly, using a for βCOP and a for the that Scyl1 is to for COPI proteins. The of Scyl1 to the of COPI-mediated membrane is the thus to determine a of Scyl1 was to the using a of this compartment S. J. J. Cell Biol. PubMed Scopus Google Scholar, A. Cell Mol. Sci. PubMed Scopus Google Scholar). was seen in a with is in with Scyl1 in the the of the the of and was seen to with Scyl1 a of Scyl1 is to the Scyl1 to the of the Scyl1 the function of to a of COPI from of the ER S. J. J. Cell Biol. PubMed Scopus Google Scholar, J. Bonifacino J.S. Cell. Full Text PDF PubMed Scopus Google and as in referred to as which are the S. J. J. Cell Biol. PubMed Scopus Google Scholar, J. E. M. G. 2000; PubMed Scopus Google Scholar). a was seen to with a in the Scyl1 and with in were seen for Scyl1 is with and is with in the data demonstrate that Scyl1 is to the and in an Arf1-independent Scyl1 COPI-mediated of the of is M. H. T. Mol. Biol. PubMed Scopus Google Scholar). The interaction of Scyl1 with COPI and localization to to the protein is involved in this pathway using a of function identified that to of Scyl1 thus used in with a to for trafficking transmembrane domain ER that COPI binding to in COPI C-terminal KDEL to the which to the ER R. T. Trends Cell Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). The the ER and the at the of at the of receptor that retrograde trafficking in the ER to a used J. J. D. J. J. Cell Biol. PubMed Scopus Google Scholar, J.S. S.Y. S. H. L. M. D. A. EMBO J. 2005; PubMed Scopus Google Scholar, J.S. S.Y. M. S. P.A. J. Cell Biol. 2002; PubMed Scopus Google Scholar) to retrograde with the localization at the which is at the the receptor is found in the compartment of Scyl1 at both the and the a in the of in Scyl1 the anterograde traffic of from the ER to the To the retrograde trafficking we a a a protein to ER trafficking as the at a J. J. D. J. J. Cell Biol. PubMed Scopus Google Scholar). for Scyl1 and demonstrate at the the with an a a The to 1 in and is from the used in and in Scyl1 was seen in with the Scyl1 this we for retrograde trafficking of the with the as by a of the at the the a in retrograde trafficking as at the at the of the confirmed a of Scyl1 data are with a for Scyl1 in COPI-mediated retrograde in Scyl1 are responsible for mdf that model of neuromuscular and spinocerebellar the in which Scyl1 are Scyl1 indirectly implicated in several including of function and clathrin-mediated endocytosis (10Schmid E.M. Ford M.G. Burtey A. Praefcke G.J. Peak-Chew S.Y. Mills I.G. Benmerah A. McMahon H.T. PLoS Biol. 2006; 4: PubMed Scopus Google Scholar, L. E. H. M. E. M. 2005; PubMed Scopus Google Scholar, M. H. 2002; PubMed Scopus Google Scholar). we demonstrate that of Scyl1, which the of Scyl1 in mdf mice, to in retrograde trafficking of the with this Scyl1 binds to COPI components in pull-down and co-immunoprecipitates with βCOP from Scyl1 co-localizes with βCOP at the and the cis-Golgi, sites of COPI-mediated membrane budding. The of Scyl1 seen with the used in this is as of Scyl1 an of βCOP of Scyl1 as the result of a in the mdf mouse (3Schmidt W.M. Kraus C. Hoger H. Hochmeister S. Oberndorfer F. Branka M. Bingemann S. Lassmann H. Muller M. Macedo-Souza L.I. Vainzof M. Zatz M. Reis A. Bittner R.E. EMBO Rep. 2007; 8: 691-697Crossref PubMed Scopus (55) Google Scholar) in Scyl1 that Scyl1 as an accessory protein to COPI-mediated The of is by a of accessory Cell Biol. 2006; PubMed Scopus Google Scholar, P.S. A. G. J. and and in Scholar). that the of and vesicles are and H.T. Mills I.G. Cell Biol. PubMed Scopus Google it is to that accessory to and Scyl1 and Scy1-like which in at the M. Ungewickell E.J. Mol. Biol. Cell. 2006; 17: 4513-4525Crossref PubMed Google an the Scyl1 function in COPI trafficking is it be that there are Scyl1 expressed in and that the C-terminal motif responsible for COPI the used in this is also the Scyl1 was in this study, the that of Scyl1 have in the Scyl1 with it to the of the (10Schmid E.M. Ford M.G. Burtey A. Praefcke G.J. Peak-Chew S.Y. Mills I.G. Benmerah A. McMahon H.T. PLoS Biol. 2006; 4: PubMed Scopus Google L. L. J. T. S. J. F. and S. and Scyl1 to alterations in the of L. E. H. M. E. M. 2005; PubMed Scopus Google Scholar). it that Scyl1 in clathrin-mediated Scyl1 was in a of vesicles A. J. Bell A.W. J. S. H. L. M. J. R.E. T. Cell. 2006; Full Text Full Text PDF PubMed Scopus Google Scholar). there are in membrane with a are identified by of the compartment by for F. S. Girard M. A. Legendre-Guillemin V. L. Boismenu D. R.E. Bell A.W. McPherson P.S. Sci. S. A. PubMed Scopus Google Scholar). as an accessory protein for COPI Scyl1 be with the from which COPI coats with the vesicles it be with the and accessory are involved in they are F. S. Girard M. A. Legendre-Guillemin V. L. Boismenu D. R.E. Bell A.W. McPherson P.S. Sci. S. A. PubMed Scopus Google Scholar). The function of Scyl1 in COPI trafficking is that it with it is to in the of COPI components to in with Scyl1 function to the of involved in COPI for the of COPI vesicles J. Trends Cell Biol. 2006; Full Text Full Text PDF PubMed Scopus Google in which the C-terminal KKXX-COO- motif the of transmembrane COPI vesicles with COPI M. J. S. A. T. J. Cell Biol. PubMed Scopus Google Scholar). of the KKXX-COO- in which the are found at the and also transmembrane interaction with COPI coats A. D. M. R. Mol. Biol. Cell. PubMed Scopus Google Scholar). Scyl1 in the and of the to binding to is with the of the which is to that to and in the from the of Scyl1 binding to COPI coats. Scyl1 for binding to C-terminal have to function in COPI binding in the of transmembrane T. Mol. Cell. Biol. 2000; PubMed Scopus Google Scholar, J. S. T. T. J. Cell Biol. PubMed Scopus Google Scholar). Scyl1 transmembrane there is a of the protein that is found in the and the of the protein from with Scyl1 a unique a C-terminal COPI-binding motif is in a to that have to be involved in the binding of the protein, of to V. D. Mol. Biol. Cell. 2000; PubMed Scopus Google Scholar). that the the domain of Scyl1 to COPI The of binding for the Scyl1 motif is The binding for KKXX-COO- in transmembrane to C. Sci. S. A. PubMed Scopus Google Scholar) the domain of A. D. M. R. Mol. Biol. Cell. PubMed Scopus Google and this the motif is found in transmembrane ER J. M. J. F. Mol. Cell. Biol. 2006; 26: PubMed Scopus Google Scholar). The motif binds to the domain of A. D. M. R. Mol. Biol. Cell. PubMed Scopus Google Scholar). in COPI-binding have the of interaction with COPI is thus that the data that the motif in Scyl1 a COPI coats that used by the they have binding motif for COPI binding is the motif H. EMBO Rep. 2005; PubMed Scopus Google Scholar). to the (in which and H. EMBO Rep. 2005; PubMed Scopus Google Scholar). the for was identified as of a of and a in βCOP Schmid V. J. T. A. J. Cell Biol. 2007; PubMed Scopus (55) Google Scholar). the Scyl1 motif the KKXX-COO- the and the motif as a motif for binding to COPI coats. of interaction is of the in which a of including and the of the P.S. Mol. Neurobiol. 2005; PubMed Google Scholar, Ford M.G. Schmid E.M. Mills I.G. McMahon H.T. Praefcke G.J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). the the COPI is and of the of is that a protein responsible for a neurodegenerative disease in the COPI trafficking in that function in trafficking have linked to a of neurodegenerative protein which was implicated in the of disease with as a binding partner for C. M. PubMed Scopus Google is a protein that in neurons M. Legendre-Guillemin V. L. V. A. McPherson P.S. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, M. L. J. E. R. Legendre-Guillemin V. M. C. M. McPherson P.S. A. EMBO J. PubMed Scopus Google Scholar). are a and of that are to and are by progressive and degeneration of motor neurons Neurol. Rep. 2006; PubMed Scopus Google Scholar). have to disease G. G. 2006; PubMed Scopus Google and several of the disease gene to trafficking C. C. 2006; PubMed Scopus Google Scholar). linked to clathrin-mediated endocytosis R. J. C. Biochem. Biophys. 2005; PubMed Scopus Google and and to and are thought to function in trafficking C. H. H. S. PubMed Scopus Google Scholar, E. J. S. Mol. 2005; PubMed Scopus Google Scholar, S. A. E. Mol. 2006; PubMed Scopus Google Scholar). most to this is the transmembrane 1 which is to the and the A. J. M. R. C. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, M. A. M. A. T. E. C. A. C. A. A. M. Mol. Cell. 2007; PubMed Scopus Google Scholar, C. J. C. Mol. 17: PubMed Scopus Google Scholar). Interestingly, of 1 with disease mutations disrupts at the ER the of ER vesicles to the A. J. M. R. C. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) and to alterations in ER and M. A. M. A. T. E. C. A. C. A. A. M. Mol. Cell. 2007; PubMed Scopus Google Scholar, C. J. C. Mol. 17: PubMed Scopus Google Scholar). have linked the COPI pathway to neurodegenerative COPI trafficking is to and of the pathway in M. T. R. PubMed Scopus Google Scholar, E. M. J. Cell Biol. PubMed Scopus Google of in the pathway COPI trafficking to a that is that that the COPI trafficking for motor neurons of protein and are be to by a in the of the COPI Our the for a of COPI and the of in disease. are to for the of Scyl1 also and for βCOP and for for and and for also and for and with

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.