| Structural highlights
Function
[GORS2_MOUSE] Plays a role in assembly and membrane stacking of the Golgi cisternae, and in the process by which Golgi stacks reform after mitotic breakdown. May regulate the intracellular transport and presentation of a defined set of transmembrane proteins, such as transmembrane TGFA.[1] [JAM3_MOUSE] Participates in cell-cell adhesion. It is a counter-receptor for ITGAM mediating leukocyte-platelet interactions and is involved in the regulation of transepithelial migration of polymorphonuclear neutrophils (PMN) (By similarity). The soluble form is a mediator of angiogenesis.[2] [3] [4]
Publication Abstract from PubMed
Spermatogenesis is a dynamic process that is regulated by adhesive interactions between germ and Sertoli cells. Germ cells express the Junctional Adhesion Molecule-C (JAM-C, encoded by Jam3), which localizes to germ/Sertoli cell contacts. JAM-C is involved in germ cell polarity and acrosome formation. Using a proteomic approach, we demonstrated that JAM-C interacted with the Golgi reassembly stacking protein of 55 kDa (GRASP55, encoded by Gorasp2) in developing germ cells. Generation and study of Gorasp2-/- mice revealed that knock-out mice suffered from spermatogenesis defects. Acrosome formation and polarized localization of JAM-C in spermatids were altered in Gorasp2-/- mice. In addition, Golgi morphology of spermatocytes was disturbed in Gorasp2-/- mice. Crystal structures of GRASP55 in complex with JAM-C or JAM-B revealed that GRASP55 interacted via PDZ-mediated interactions with JAMs and induced a conformational change in GRASP55 with respect of its free conformation. An in silico pharmacophore approach identified a chemical compound called Graspin that inhibited PDZ-mediated interactions of GRASP55 with JAMs. Treatment of mice with Graspin hampered the polarized localization of JAM-C in spermatids, induced the premature release of spermatids and affected the Golgi morphology of meiotic spermatocytes.
Genetic, structural, and chemical insights into the dual function of GRASP55 in germ cell Golgi remodeling and JAM-C polarized localization during spermatogenesis.,Cartier-Michaud A, Bailly AL, Betzi S, Shi X, Lissitzky JC, Zarubica A, Serge A, Roche P, Lugari A, Hamon V, Bardin F, Derviaux C, Lembo F, Audebert S, Marchetto S, Durand B, Borg JP, Shi N, Morelli X, Aurrand-Lions M PLoS Genet. 2017 Jun 15;13(6):e1006803. doi: 10.1371/journal.pgen.1006803., eCollection 2017 Jun. PMID:28617811[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Shorter J, Watson R, Giannakou ME, Clarke M, Warren G, Barr FA. GRASP55, a second mammalian GRASP protein involved in the stacking of Golgi cisternae in a cell-free system. EMBO J. 1999 Sep 15;18(18):4949-60. PMID:10487747 doi:http://dx.doi.org/10.1093/emboj/18.18.4949
- ↑ Aurrand-Lions M, Johnson-Leger C, Wong C, Du Pasquier L, Imhof BA. Heterogeneity of endothelial junctions is reflected by differential expression and specific subcellular localization of the three JAM family members. Blood. 2001 Dec 15;98(13):3699-707. PMID:11739175
- ↑ Lamagna C, Hodivala-Dilke KM, Imhof BA, Aurrand-Lions M. Antibody against junctional adhesion molecule-C inhibits angiogenesis and tumor growth. Cancer Res. 2005 Jul 1;65(13):5703-10. PMID:15994945 doi:http://dx.doi.org/10.1158/0008-5472.CAN-04-4012
- ↑ Rabquer BJ, Amin MA, Teegala N, Shaheen MK, Tsou PS, Ruth JH, Lesch CA, Imhof BA, Koch AE. Junctional adhesion molecule-C is a soluble mediator of angiogenesis. J Immunol. 2010 Aug 1;185(3):1777-85. doi: 10.4049/jimmunol.1000556. Epub 2010, Jun 30. PMID:20592283 doi:10.4049/jimmunol.1000556
- ↑ Cartier-Michaud A, Bailly AL, Betzi S, Shi X, Lissitzky JC, Zarubica A, Serge A, Roche P, Lugari A, Hamon V, Bardin F, Derviaux C, Lembo F, Audebert S, Marchetto S, Durand B, Borg JP, Shi N, Morelli X, Aurrand-Lions M. Genetic, structural, and chemical insights into the dual function of GRASP55 in germ cell Golgi remodeling and JAM-C polarized localization during spermatogenesis. PLoS Genet. 2017 Jun 15;13(6):e1006803. doi: 10.1371/journal.pgen.1006803., eCollection 2017 Jun. PMID:28617811 doi:http://dx.doi.org/10.1371/journal.pgen.1006803
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