| Structural highlights
Function
[PLXD1_MOUSE] Cell surface receptor for SEMA4A and for class 3 semaphorins, such as SEMA3A, SEMA3C and SEMA3E. Plays an important role in cell-cell signaling, and in regulating the migration of a wide spectrum of cell types. Regulates the migration of thymocytes in the medulla. Regulates endothelial cell migration. Plays an important role in ensuring the specificity of synapse formation. Mediates anti-angiogenic signaling in response to SEMA3E. Required for normal development of the heart and vasculature.[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
The GIPC family adaptor proteins mediate endocytosis by tethering cargo proteins to the myosin VI motor. The structural mechanisms for the GIPC/cargo and GIPC/myosin VI interactions remained unclear. PlexinD1, a transmembrane receptor that regulates neuronal and cardiovascular development, is a cargo of GIPCs. GIPC-mediated endocytic trafficking regulates PlexinD1 signaling. Here, we unravel the mechanisms of the interactions among PlexinD1, GIPCs and myosin VI by a series of crystal structures of these proteins in apo or bound states. GIPC1 forms a domain-swapped dimer in an autoinhibited conformation that hinders binding of both PlexinD1 and myosin VI. PlexinD1 binding to GIPC1 releases the autoinhibition, promoting its interaction with myosin VI. GIPCs and myosin VI interact through two distinct interfaces and form an open-ended alternating array. Our data support that this alternating array underlies the oligomerization of the GIPC/Myosin VI complexes in solution and cells.
Structure analyses reveal a regulated oligomerization mechanism of the PlexinD1/GIPC/myosin VI complex.,Shang G, Brautigam CA, Chen R, Lu D, Torres-Vazquez J, Zhang X Elife. 2017 May 24;6. pii: e27322. doi: 10.7554/eLife.27322. PMID:28537552[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gitler AD, Lu MM, Epstein JA. PlexinD1 and semaphorin signaling are required in endothelial cells for cardiovascular development. Dev Cell. 2004 Jul;7(1):107-16. PMID:15239958 doi:http://dx.doi.org/10.1016/j.devcel.2004.06.002
- ↑ Toyofuku T, Yabuki M, Kamei J, Kamei M, Makino N, Kumanogoh A, Hori M. Semaphorin-4A, an activator for T-cell-mediated immunity, suppresses angiogenesis via Plexin-D1. EMBO J. 2007 Mar 7;26(5):1373-84. Epub 2007 Feb 22. PMID:17318185 doi:http://dx.doi.org/10.1038/sj.emboj.7601589
- ↑ Zhang Y, Singh MK, Degenhardt KR, Lu MM, Bennett J, Yoshida Y, Epstein JA. Tie2Cre-mediated inactivation of plexinD1 results in congenital heart, vascular and skeletal defects. Dev Biol. 2009 Jan 1;325(1):82-93. doi: 10.1016/j.ydbio.2008.09.031. Epub 2008, Oct 17. PMID:18992737 doi:http://dx.doi.org/10.1016/j.ydbio.2008.09.031
- ↑ Choi YI, Duke-Cohan JS, Ahmed WB, Handley MA, Mann F, Epstein JA, Clayton LK, Reinherz EL. PlexinD1 glycoprotein controls migration of positively selected thymocytes into the medulla. Immunity. 2008 Dec 19;29(6):888-98. doi: 10.1016/j.immuni.2008.10.008. Epub 2008 , Nov 27. PMID:19027330 doi:http://dx.doi.org/10.1016/j.immuni.2008.10.008
- ↑ Pecho-Vrieseling E, Sigrist M, Yoshida Y, Jessell TM, Arber S. Specificity of sensory-motor connections encoded by Sema3e-Plxnd1 recognition. Nature. 2009 Jun 11;459(7248):842-6. doi: 10.1038/nature08000. Epub 2009 May 6. PMID:19421194 doi:http://dx.doi.org/10.1038/nature08000
- ↑ Ding JB, Oh WJ, Sabatini BL, Gu C. Semaphorin 3E-Plexin-D1 signaling controls pathway-specific synapse formation in the striatum. Nat Neurosci. 2011 Dec 18;15(2):215-23. doi: 10.1038/nn.3003. PMID:22179111 doi:http://dx.doi.org/10.1038/nn.3003
- ↑ Shang G, Brautigam CA, Chen R, Lu D, Torres-Vazquez J, Zhang X. Structure analyses reveal a regulated oligomerization mechanism of the PlexinD1/GIPC/myosin VI complex. Elife. 2017 May 24;6. pii: e27322. doi: 10.7554/eLife.27322. PMID:28537552 doi:http://dx.doi.org/10.7554/eLife.27322
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