A Novel Family of Apicomplexan Glideosome-associated Proteins with an Inner Membrane-anchoring Role

The phylum Apicomplexa are a group of obligate intracellular parasites responsible for a wide range of important diseases. Central to the lifecycle of these unicellular parasites is their ability to migrate through animal tissue and invade target host cells. Apicomplexan movement is generated by a unique system of gliding motility in which substrate adhesins and invasion-related proteins are pulled across the plasma membrane by an underlying actin-myosin motor. The myosins of this motor are inserted into a dual membrane layer called the inner membrane complex (IMC) that is sandwiched between the plasma membrane and an underlying cytoskeletal basket. Central to our understanding of gliding motility is the characterization of proteins residing within the IMC, but to date only a few proteins are known. We report here a novel family of six-pass transmembrane proteins, termed the GAPM family, which are highly conserved and specific to Apicomplexa. In Plasmodium falciparum and Toxoplasma gondii the GAPMs localize to the IMC where they form highly SDS-resistant oligomeric complexes. The GAPMs co-purify with the cytoskeletal alveolin proteins and also to some degree with the actin-myosin motor itself. Hence, these proteins are strong candidates for an IMC-anchoring role, either directly or indirectly tethering the motor to the cytoskeleton. The phylum Apicomplexa are a group of obligate intracellular parasites responsible for a wide range of important diseases. Central to the lifecycle of these unicellular parasites is their ability to migrate through animal tissue and invade target host cells. Apicomplexan movement is generated by a unique system of gliding motility in which substrate adhesins and invasion-related proteins are pulled across the plasma membrane by an underlying actin-myosin motor. The myosins of this motor are inserted into a dual membrane layer called the inner membrane complex (IMC) that is sandwiched between the plasma membrane and an underlying cytoskeletal basket. Central to our understanding of gliding motility is the characterization of proteins residing within the IMC, but to date only a few proteins are known. We report here a novel family of six-pass transmembrane proteins, termed the GAPM family, which are highly conserved and specific to Apicomplexa. In Plasmodium falciparum and Toxoplasma gondii the GAPMs localize to the IMC where they form highly SDS-resistant oligomeric complexes. The GAPMs co-purify with the cytoskeletal alveolin proteins and also to some degree with the actin-myosin motor itself. Hence, these proteins are strong candidates for an IMC-anchoring role, either directly or indirectly tethering the motor to the cytoskeleton. Apicomplexan parasites cause a multitude of illnesses through infection of both human and livestock hosts. Members of this phylum include the opportunistic human parasites Toxoplasma gondii and Cryptosporidium parvum, pathogens of livestock, including Theileria annulata and Eimeria tenalla, and most notably the Plasmodium species, the causative agents of malaria in humans. Infection with P. falciparum results in ∼1–3 million deaths and a further 500 million infections annually (1Snow R.W. Guerra C.A. Noor A.M. Myint H.Y. Hay S.I. Nature. 2005; 434: 214-217Crossref PubMed Scopus (2138) Google Scholar). During various stages of the Apicomplexan lifecycle the parasites require motility to migrate through their insect and vertebrate hosts and to invade and internalize themselves within targeted host cells (2Baum J. Gilberger T.W. Frischknecht F. Meissner M. Trends Parasitol. 2008; 24: 557-563Abstract Full Text Full Text PDF PubMed Scopus (139) Google Scholar, 3Cowman A.F. Crabb B.S. Cell. 2006; 124: 755-766Abstract Full Text Full Text PDF PubMed Scopus (662) Google Scholar, 4Tardieux I. Ménard R. Traffic. 2008; 9: 627-635Crossref PubMed Scopus (33) Google Scholar). The parasite's unique mechanism of gliding motility is powered by an Apicomplexan-specific motor complex termed the actin-myosin motor (5Keeley A. Soldati D. Trends Cell Biol. 2004; 14: 528-532Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar), which resides between the outer plasma membrane and inner membrane complex (IMC) 4The abbreviations used are:IMCinner membrane complexDRMdetergent-resistant membraneHAhemagglutininGFPgreen fluorescent proteinRIPAradioimmune precipitation assaybis-tris2-[bis(2-hydroxyethyl)amino]-2-(hydroxymethyl)propane-1,3-diolmAbmonoclonal antibodyChFPcherry fluorescent proteinDSPdithiobis succinimidyl propionateIMPintramembranous particleALValveolinGPIglycosylphosphatidylinositol. (6Soldati D. Meissner M. Curr. Opin Cell Biol. 2004; 16: 32-40Crossref PubMed Scopus (95) Google Scholar). The IMC is a continuous patchwork of flattened vesicular cisternae located directly beneath the plasma membrane and overlying the cytoskeletal network (7Bergman L.W. Kaiser K. Fujioka H. Coppens I. Daly T.M. Fox S. Matuschewski K. Nussenzweig V. Kappe S.H. J. Cell Sci. 2003; 116: 39-49Crossref PubMed Scopus (157) Google Scholar, 8Pinder J.C. Fowler R.E. Dluzewski A.R. Bannister L.H. Lavin F.M. Mitchell G.H. Wilson R.J. Gratzer W.B. J. Cell Sci. 1998; 111: 1831-1839Crossref PubMed Google Scholar). The IMC appears to arise from Golgi-associated vesicles flattened during parasite maturation to form large membranous sheets, which envelope the parasite and leave only a small gap at the extreme parasite apex (9Bannister L.H. Hopkins J.M. Fowler R.E. Krishna S. Mitchell G.H. Parasitology. 2000; 121: 273-287Crossref PubMed Scopus (91) Google Scholar). inner membrane complex detergent-resistant membrane hemagglutinin green fluorescent protein radioimmune precipitation assay 2-[bis(2-hydroxyethyl)amino]-2-(hydroxymethyl)propane-1,3-diol monoclonal antibody cherry fluorescent protein dithiobis succinimidyl propionate intramembranous particle alveolin glycosylphosphatidylinositol. The myosin component of the actin-myosin motor has previously been defined as a tetrameric complex consisting of a class XIV myosin termed Myo-A (10Pinder J. Fowler R. Bannister L. Dluzewski A. Mitchell G.H. Parasitol Today. 2000; 16: 240-245Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar), a myosin tail interacting protein (also called myosin light chain) (7Bergman L.W. Kaiser K. Fujioka H. Coppens I. Daly T.M. Fox S. Matuschewski K. Nussenzweig V. Kappe S.H. J. Cell Sci. 2003; 116: 39-49Crossref PubMed Scopus (157) Google Scholar) and the two glideosome-associated proteins GAP45 and GAP50 (11Gaskins E. Gilk S. DeVore N. Mann T. Ward G. Beckers C. J. Cell Biol. 2004; 165: 383-393Crossref PubMed Scopus (206) Google Scholar). These motor components are linked to the outer IMC membrane via the membrane proteins GAP45/50 (11Gaskins E. Gilk S. DeVore N. Mann T. Ward G. Beckers C. J. Cell Biol. 2004; 165: 383-393Crossref PubMed Scopus (206) Google Scholar). Between the plasma membrane and the IMC are actin filaments held in place through aldolase-mediated contact with the C-terminal tails of plasma membrane-spanning adhesive proteins whose ectodomains bind substrate and host cells (2Baum J. Gilberger T.W. Frischknecht F. Meissner M. Trends Parasitol. 2008; 24: 557-563Abstract Full Text Full Text PDF PubMed Scopus (139) Google Scholar). To power the forward movement of apicomplexan zoite stages, myosin pulls the actin filaments and their attached adhesins rearward. For this to succeed the GAP-myosin complex must presumably be fixed to the IMC, possibly via interactions with unidentified proteins linking the motor to the underlying cytoskeleton. Studies of fluorescently tagged GAP50 confirm it is relatively immobile within the IMC, however attempts to identify potential anchoring proteins have not been successful and have instead indicated that GAP50 may be immobilized by the lipid-raft like properties of the IMC membranes (12Johnson T.M. Rajfur Z. Jacobson K. Beckers C.J. Mol. Biol. Cell. 2007; 18: 3039-3046Crossref PubMed Scopus (61) Google Scholar). The actin-myosin complex is confined to the outer IMC membrane while the opposing innermost IMC membrane is studded with 9 nm intramembranous particles, revealed by electron microscopy of freeze fractured Toxoplasma tachyzoites and Plasmodium ookinetes (13Morrissette N.S. Murray J.M. Roos D.S. J. Cell Sci. 1997; 110: 35-42Crossref PubMed Google Scholar, 14Raibaud A. Lupetti P. Paul R.E. Mercati D. Brey P.T. Sinden R.E. Heuser J.E. Dallai R. J. Struct. Biol. 2001; 135: 47-57Crossref PubMed Scopus (45) Google Scholar). The size of these particles suggests that the proteins involved are likely to form high molecular weight complexes that overlay the parasite's cytoskeletal network and possibly anchor the IMC to the cytoskeleton (12Johnson T.M. Rajfur Z. Jacobson K. Beckers C.J. Mol. Biol. Cell. 2007; 18: 3039-3046Crossref PubMed Scopus (61) Google Scholar, 13Morrissette N.S. Murray J.M. Roos D.S. J. Cell Sci. 1997; 110: 35-42Crossref PubMed Google Scholar, 14Raibaud A. Lupetti P. Paul R.E. Mercati D. Brey P.T. Sinden R.E. Heuser J.E. Dallai R. J. Struct. Biol. 2001; 135: 47-57Crossref PubMed Scopus (45) Google Scholar, 15Mann T. Beckers C. Mol. Biochem. Parasitol. 2001; 115: 257-268Crossref PubMed Scopus (184) Google Scholar). Due to the close of the inner and outer IMC membranes A. Lupetti P. Paul R.E. Mercati D. Brey P.T. Sinden R.E. Heuser J.E. Dallai R. J. Struct. Biol. 2001; 135: 47-57Crossref PubMed Scopus (45) Google Scholar, S. Beckers C.J. 2008; PubMed Scopus Google Scholar), it is that the intramembranous particles the IMC and with the GAP-myosin complex to within the To identify proteins that be components of the intramembranous particles, from the detergent-resistant membrane of P. falciparum parasites T. L. Crabb B.S. J. Biol. 2005; Full Text Full Text PDF PubMed Scopus Google Scholar, T. Crabb B.S. Mol. Biochem. Parasitol. 2007; PubMed Scopus Google Scholar). or of they to proteins involved in host as also indicated that P. falciparum the IMC proteins T. L. Crabb B.S. J. Biol. 2005; Full Text Full Text PDF PubMed Scopus Google Scholar), and in T. gondii have also that the IMC is in (12Johnson T.M. Rajfur Z. Jacobson K. Beckers C.J. Mol. Biol. Cell. 2007; 18: 3039-3046Crossref PubMed Scopus (61) Google Scholar). indicated that P. falciparum protein complexes by a and as as a novel six-pass transmembrane protein T. Crabb B.S. Mol. Biochem. Parasitol. 2007; PubMed Scopus Google Scholar). protein to six-pass transmembrane protein previously in P. falciparum T. L. Crabb B.S. J. Biol. 2005; Full Text Full Text PDF PubMed Scopus Google Scholar). We here that and termed and protein with to a family of proteins specific to the Apicomplexa and that P. falciparum GAPM proteins, and their in T. localize to the parasite The GAPMs form high molecular weight complexes that are to and by a of and be components of the intramembranous particles in electron by the GAPM complexes co-purify with components of the actin-myosin motor and the parasite cytoskeletal network GAPMs anchor the IMC to the cytoskeleton and a in tethering the motor to cytoskeleton. of and by of the and and are in The GAPM proteins with 2004; PubMed Scopus Google Scholar), the and with of of also from either P. falciparum parasites or T. gondii parasites in into the and by The P. falciparum with and into the of a of T. Crabb B.S. Mol. 2008; PubMed Scopus Google Scholar, M. E. Soldati D. Crabb B.S. Sci. 2005; PubMed Scopus Google Scholar), called and to with a and called and and from with and and into to a with and the called is a of in which has been with the C. S. Sci. S. A. 2008; PubMed Scopus Google Scholar). P. falciparum parasites with either of or and PubMed Scopus Google Scholar). with nm B.S. M. Gilberger T.W. T. A.F. Mol. Biol. 2004; Google Scholar). T. gondii parasites with M. Soldati D. Roos D.S. Mol. Biochem. Parasitol. 1998; PubMed Scopus Google Scholar) and in human and cells. of to of P. falciparum parasites with in to from the cells. The by the parasite in at for in either in or proteins from the by in a at for of the as as the in in at to further the to protein with at not at for to T. gondii tachyzoites by in and with either or in and or to with specific from J. D. J. M. Z. Gilberger T.W. A.F. J. Biol. 2006; Full Text Full Text PDF PubMed Scopus Google Scholar), J. D. J. M. Z. Gilberger T.W. A.F. J. Biol. 2006; Full Text Full Text PDF PubMed Scopus Google Scholar), J. D. J. M. Z. Gilberger T.W. A.F. J. Biol. 2006; Full Text Full Text PDF PubMed Scopus Google Scholar), from or from and nm from antibody with microscopy P. falciparum and T. gondii with For parasites fixed in either or and with the antibody and either J. D. J. M. Z. Gilberger T.W. A.F. J. Biol. 2006; Full Text Full Text PDF PubMed Scopus Google Scholar) or nm and nm with as previously Ward PubMed Scopus (61) Google Scholar). parasites fixed in and with and from For and parasites as as and parasites by in with and either or and to the and the at for For with of the and parasites as or to the for at to the and the at for proteins in or and by as as P. falciparum or parasites as and in of dithiobis succinimidyl propionate for in in and either of or proteins and with transmembrane previously in from P. falciparum T. L. Crabb B.S. J. Biol. 2005; Full Text Full Text PDF PubMed Scopus Google Scholar, T. Crabb B.S. Mol. Biochem. Parasitol. 2007; PubMed Scopus Google Scholar). of the of these proteins revealed a to degree of and of the Plasmodium C. J. J. S. A. G. M. F. J. J.C. E. V. C. Roos D.S. C. C.J. C. H. PubMed Scopus Google Scholar) indicated that P. falciparum an of the family termed proteins by A. G. J. Mol. Biol. 2001; PubMed Scopus Google Scholar) to have transmembrane with the and C-terminal tails and and the of the membrane for the and and the for of the Apicomplexan C. M. H. Z. S. P. J. E. C.J. Roos D.S. J.C. 2007; PubMed Scopus Google Scholar) revealed that most Apicomplexan also of the GAPM of their indicated that of these proteins into of which have called and T. gondii two in and and and and and and protein of revealed of the GAPM family the Apicomplexan GAPM revealed of across the GAPM family as as within the and of the the the transmembrane that two and are highly conserved across Apicomplexa. and are a high of in and suggests that these may in GAPM or interactions with the and to be highly conserved within but not between of the GAPM and may group specific To fluorescent and of GAPMs in the of to the proteins, from of the in both P. falciparum and T. gondii tagged at their with either green fluorescent protein cherry fluorescent protein 2006; PubMed Scopus Google Scholar) a hemagglutinin For the GAPMs in P. in and with the of or a The inserted into a of the M. E. Soldati D. Crabb B.S. Sci. 2005; PubMed Scopus Google Scholar) In this system the of be by the of the and by the the of a protein whose is in by a protein T. Crabb B.S. Mol. 2008; PubMed Scopus Google Scholar, M. E. Soldati D. Crabb B.S. Sci. 2005; PubMed Scopus Google Scholar). of the of the the also during Z. M. J. Biol. 2003; PubMed Scopus Google Scholar, L. A. M. 2004; 14: PubMed Scopus Google Scholar). parasite with the and the proteins by only for the and and only in a of and this in the of which have indicated that the the may have into the the with of parasites this The parasites and further with this instead to the These by microscopy with a monoclonal antibody used for in the protein and also into the parasites but not by the and the not of proteins possibly to some To in which membrane the GAPMs P. falciparum by In Plasmodium stages, by where of and within a by a plasma are in the We and the are from the plasma with and either the antibody or parasite plasma antibody for the C-terminal of protein The of and from that of and from that of plasma membrane protein and microscopy of and an IMC to that of and and a of is in To the GAPMs localize to the IMC in the GAPMs of T. gondii by The of and to a of both cherry fluorescent protein and the The into the the of the during the of the proteins the of tachyzoites within host cells The GAPMs in membranous of the cells of IMC To confirm T. gondii parasites with which the parasite membrane from the underlying IMC Ward PubMed Scopus (61) Google Scholar). parasites fixed and with specific to the parasite plasma membrane and the protein parasites outer only in the of the parasite IMC To that the GAPM proteins and been tagged as the P. falciparum these proteins by The cells with to host proteins, and the in protein and the of the proteins revealed the and as as high molecular for not The of these proteins to further and as and in of to the of the of the and of the strong and the and by and to by the with or The with of the proteins with their indicated the of in in and with the and the most and in also by the the and for The of proteins also motor components and by and only a small of these proteins in the in and To the of the to a to the alveolin family of cytoskeletal proteins of the a group of that include and A.F. Mol. Biol. 2008; PubMed Scopus Google Scholar). The Plasmodium alveolin antibody that at and which to the and A.F. Mol. Biol. 2008; PubMed Scopus Google Scholar), that are in stages M. P. S. 2003; PubMed Scopus Google Scholar, Z. M. J. Biol. 2003; PubMed Scopus Google Scholar). The of these are and the proteins migrate which has been previously for the of A.F. Mol. Biol. 2008; PubMed Scopus Google Scholar). the of the to and in that they only with the and and the and for The of some of the proteins to in and to in that the proteins be components of complexes within the To this parasites with the dithiobis succinimidyl propionate host proteins been by The parasites in a and the by to the in the and also to of the of the with and indicated that most proteins that previously been to and which previously been to and in that to in of that the proteins from complexes of to also only in as a high molecular weight that it complexes The only proteins that in the molecular weight and These have been and from large complexes or have been from proteins that not into the IMC complexes. to the of GAPM proteins in T. gondii These revealed that the Toxoplasma proteins to of Plasmodium in not only but also in their to into like is the most and are the and and are and the Toxoplasma GAPM to their Plasmodium The of GAPM protein in to their large that they may a within the IMC as the membranes anchoring the actin-myosin motor or linking the IMC to the cytoskeleton. To potential interactions between the GAPM proteins and parasite proteins, from parasites in it the GAPM protein between the and the with and the by unique to but not and their by protein from a of the proteins proteins that and protein this be a it has been in with the IMC to host to presumably to the actin-myosin motor S. Beckers C.J. 2008; PubMed Scopus Google Scholar). The be in the proteins with a involved in and have been involved in IMC The parasite proteins highly To the interactions of the GAPMs with the actin-myosin motor and alveolin of GAPM with For P. with for in which used with either the or the antibody that the successful in parasites but not in parasites To IMC proteins the with and These in the but not in the The GAP45 and GAP50 in the and and the in and is of the GAPM proteins from the of the GAP45/50 proteins that only a of the actin-myosin motor components be interacting with the or that the interactions between the proteins have been by the of with the also by with antibody a in to in GAPMs in the precipitation that be and and of the in the degree of between the with the most as as the with a of proteins from to in the for both and and The of these are the used to the proteins have the complexes. We that the high of proteins the during the may have the proteins to further their to into and To T. gondii GAPMs also of the actin-myosin T. gondii parasites GAPM proteins used in as These by that revealed also while parasites at and for of the also in this not a Toxoplasma as as P. falciparum it is not to which specific interacting with the We however that previously with a antibody A.F. Mol. Biol. 2008; PubMed Scopus Google Scholar). for only a small of the and proteins in the We to interactions with to a of antibody to this To the interactions between the GAPM proteins and the actin-myosin and to with their in not in P. falciparum GAPM and with either or complexes with specific to small of and and of these proteins with of a between the GAPMs and the between the GAPMs and and with and GAP45 to in The GAPMs in this a family of six-pass transmembrane proteins in Apicomplexa. In the Plasmodium and Toxoplasma the GAPMs localize to the IMC that the of Apicomplexan zoite stages these proteins are of this phylum that GAPMs Apicomplexan-specific The tagged GAPMs with the cytoskeletal and to a degree the actin-myosin motor components suggests that the GAPMs as protein that the IMC to the cytoskeleton or as protein that the IMC to and the myosin complex the cytoskeleton have attempts to identify of the complex to identify the GAPMs (11Gaskins E. Gilk S. DeVore N. Mann T. Ward G. Beckers C. J. Cell Biol. 2004; 165: 383-393Crossref PubMed Scopus (206) Google Scholar, T.M. Rajfur Z. Jacobson K. Beckers C.J. Mol. Biol. Cell. 2007; 18: 3039-3046Crossref PubMed Scopus (61) Google We these attempts may have the interactions of the GAPMs with GAP45/50 not the and the GAPMs are to in form by and to specific and the size of the complexes they form the GAPMs are in the IMC For to the GAPMs have to be which in their in the of these and it is that of the GAP45/50 and GAPM The is to the cytoskeleton and the IMC, which is also only of the with the To of the GAPMs with the and GAP45/50 with in P. in and in both We these in the of the with their These in In P. falciparum this GAP45/50 but only the for the GAPMs only with GAP45 and with of the GAPMs in the attempts to identify proteins in Toxoplasma they with and the GAPMs in this parasite are in P. falciparum (11Gaskins E. Gilk S. DeVore N. Mann T. Ward G. Beckers C. J. Cell Biol. 2004; 165: 383-393Crossref PubMed Scopus (206) Google Scholar). also used to identify proteins to the complex (12Johnson T.M. Rajfur Z. Jacobson K. Beckers C.J. Mol. Biol. Cell. 2007; 18: 3039-3046Crossref PubMed Scopus (61) Google Scholar) but as have they cause the GAPMs to the GAPM proteins be in with they may have they as high molecular weight We it to the with to the GAPMs into We the most this may have been by the highly that is as large as itself. of our P. falciparum with the and they bind to not in of our is that small of IMC of these proteins are they are to and These have to be the parasite by to We also a degree of with our that the GAPMs IMC with attached cytoskeleton. For two the only a cytoskeletal To the IMC require the of a IMC protein not to bind to the proteins as a in the but protein is known. In the have these and the that some in the are that GAPMs contact both the alveolin cytoskeleton of the IMC and the GAP-myosin complex the In of the the interactions between the GAPMs and the of the network resides the of the IMC that the GAPMs may also localize to this In the of GAPMs into highly these proteins candidates for of the family of 9 nm intramembranous particles the IMC in (6Soldati D. Meissner M. Curr. Opin Cell Biol. 2004; 16: 32-40Crossref PubMed Scopus (95) Google Scholar, 13Morrissette N.S. Murray J.M. Roos D.S. J. Cell Sci. 1997; 110: 35-42Crossref PubMed Google Scholar, 14Raibaud A. Lupetti P. Paul R.E. Mercati D. Brey P.T. Sinden R.E. Heuser J.E. Dallai R. J. Struct. Biol. 2001; 135: 47-57Crossref PubMed Scopus (45) Google Scholar, 15Mann T. Beckers C. Mol. Biochem. Parasitol. 2001; 115: 257-268Crossref PubMed Scopus (184) Google Scholar). has been that localize to of the of overlay the cytoskeletal filaments nm alveolin T. Beckers C. Mol. Biochem. Parasitol. 2001; 115: 257-268Crossref PubMed Scopus (184) Google Scholar) and a (13Morrissette N.S. Murray J.M. Roos D.S. J. Cell Sci. 1997; 110: 35-42Crossref PubMed Google Scholar). of form in the IMC or may the of the flattened vesicles that the IMC A. Lupetti P. Paul R.E. Mercati D. Brey P.T. Sinden R.E. Heuser J.E. Dallai R. J. Struct. Biol. 2001; 135: 47-57Crossref PubMed Scopus (45) Google Scholar). degree of that the GAPMs are proteins, of a To the GAPMs bind to to specific to the and C-terminal tails of to the protein with the and and the not specific have to be to the is that the and proteins in of their molecular that they be to the have been by of to form a 9 nm particle the protein complexes have to be We have microscopy to the GAPMs are components of these 9 nm particles specific for the GAPMs the IMC with a to by freeze the microscopy not successful not specific of the IMC in P. falciparum parasites not is that the used for electron microscopy may have the GAPMs to an that to the in this is our that GAPM with or is in microscopy of cells fixed in with not microscopy of the GAPMs may require The GAPM proteins to form possibly large they are to be to or the GAPM proteins in complexes The of GAPMs in the GAPMs and The large membrane particles may only bind to a small of actin-myosin complexes and alveolin the a here that the GAPM proteins form complexes the of the IMC where they with components of the interactions with the GAP45/50 it is that the of GAP50 resides within the IMC (11Gaskins E. Gilk S. DeVore N. Mann T. Ward G. Beckers C. J. Cell Biol. 2004; 165: 383-393Crossref PubMed Scopus (206) Google Scholar) and only a small of the GAP45/50 proteins be with the GAPM proteins where the GAPMs within the IMC and with to the of this important apicomplexan of We for the GAP45 and Beckers for the and Paul and for We also of the of for of the T. gondii and J. I. D. and C. L. of for the of the C. We also the and antibody and the for with

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