VARP is recruited on to endosomes by direct interaction with retromer, where together they function in export to the cell surface.
VARP is recruited on to endosomes by direct interaction with retromer, where together they function in export to the cell surface.
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DOI：
10.1016/j.devcel.2014.04.010
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发表时间：
2014-06-09
影响因子：
11.8
通讯作者：
Owen, David J.
中科院分区：
文献类型：
--
作者：
Hesketh, Geoffrey G.;Perez-Dorado, Inmaculada;Jackson, Lauren R.;Wartosch, Lena;Schaefer, Ingmar B.;Gray, Sally R.;McCoy, Airlie J.;Zeldin, Oliver B.;Garman, Elspeth F.;Harbour, Michael E.;Evans, Philip R.;Seaman, Matthew N. J.;Luzio, J. Paul;Owen, David J.
VARP是一个Rab32/38效应子，也与内体/溶酶体R-SNARE VAMP7结合。VARP结合调节VAMP7参与SNARE复合体的形成，从而影响VAMP7介导膜融合事件。不能结合Rab32：GTP的VARP突变版本，根据这里描述的VARP ankyrin Repeat/Rab32：GTP复杂结构设计，出人意料地保留了内体定位，表明VARP的招募不依赖于Rab32结合。我们发现，VARP在膜上的募集是通过与VPS29的直接相互作用而实现的，VPS29是逆聚体复合体的一个亚单位，参与了从内体到TGN和细胞表面的运输。GLUT1从内体到细胞表面的运输需要VARP、VPS29和VAMP7，并依赖于VPS29和VARP之间的直接相互作用。最后，我们认为VAMP7的内吞循环依赖于它与VARP的相互作用，因此也依赖于逆转录。VARP到内体的募集不依赖于它与Rab32的相互作用：GTP VARP包含两个锌结合的CHPLCxCxxC基序，与逆转录聚合体亚单位VPS29结合，VARP通过与VPS29的相互作用被招募到内体，逆转录聚体和VAMP7都参与GLUT1到细胞表面的运输，VAMP7结合的Rab32-效应器和Rab21egFVARP直接结合到逆转录聚合体亚单位VPS29。VARP与VPS29的相互作用将其招募到内体上，从而将货物分选反聚体复合体与参与内体功能的R-SNARE联系起来。所有这三种物质都参与了内小体到细胞表面的运输。
VARP is a Rab32/38 effector that also binds to the endosomal/lysosomal R-SNARE VAMP7. VARP binding regulates VAMP7 participation in SNARE complex formation and can therefore influence VAMP7-mediated membrane fusion events. Mutant versions of VARP that cannot bind Rab32:GTP, designed on the basis of the VARP ankyrin repeat/Rab32:GTP complex structure described here, unexpectedly retain endosomal localization, showing that VARP recruitment is not dependent on Rab32 binding. We show that recruitment of VARP to the endosomal membrane is mediated by its direct interaction with VPS29, a subunit of the retromer complex, which is involved in trafficking from endosomes to the TGN and the cell surface. Transport of GLUT1 from endosomes to the cell surface requires VARP, VPS29, and VAMP7 and depends on the direct interaction between VPS29 and VARP. Finally, we propose that endocytic cycling of VAMP7 depends on its interaction with VARP and, consequently, also on retromer. VARP recruitment to endosomes does not depend on its interaction with Rab32:GTP VARP contains two Zinc-binding CHPLCxCxxC motifs that bind the retromer subunit VPS29 VARP is recruited to endosomes through its interaction with VPS29 VARP, retromer, and VAMP7 are all involved in trafficking of GLUT1 to the cell surface The VAMP7-binding Rab32-effector and Rab21GEF VARP binds directly to the retromer subunit VPS29. VARP’s interaction with VPS29 recruits it on to endosomes, thereby linking the cargo sorting retromer complex with an R-SNARE involved in endosomal function. All three are shown to be involved in endosome to cell surface transport.
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影响因子：
16.2
作者：
Bal M;Leitz J;Reese AL;Ramirez DM;Durakoglugil M;Herz J;Monteggia LM;Kavalali ET
通讯作者：
Kavalali ET
影响因子：
5.3
作者：
Fjorback, Anja W.;Seaman, Matthew;Andersen, Olav M.
通讯作者：
Andersen, Olav M.
影响因子：
16.8
作者：
Collins, BM;Skinner, CF;Owen, DJ
通讯作者：
Owen, DJ
影响因子：
2.7
作者：
Helfer, Emmanuele;Harbour, Michael E.;Gautreau, Alexis
通讯作者：
Gautreau, Alexis
影响因子：
3.3
作者：
Jia D;Gomez TS;Billadeau DD;Rosen MK
通讯作者：
Rosen MK