Multiple Roles of VARP in Endosomal Trafficking: Rabs, Retromer Components and R-SNARE VAMP7 Meet on VARP.
VARP (VPS9-ankyrin-repeat protein, also known as ANKRD27) was originally identified as an N-terminal VPS9 (vacuolar protein sorting 9)-domain-containing protein that possesses guanine nucleotide exchange factor (GEF) activity toward small GTPase Rab21 and contains two ankyrin repeat (ANKR) domains in its central region. A number of VARP-interacting molecules have been identified during the past five years, and considerable attention is now being directed to the multiple roles of VARP in endosomal trafficking. More specifically, VARP is now known to interact with three different types of key membrane trafficking regulators, i.e. small GTPase Rabs (Rab32, Rab38 and Rab40C), the retromer complex (a sorting nexin dimer, VPS26, VPS29 and VPS35) and R-SNARE VAMP7. By binding to several of these molecules, VARP regulates endosomal trafficking, which underlies a variety of cellular events, including melanogenic enzyme trafficking to melanosomes, dendrite outgrowth of melanocytes, neurite outgrowth and retromer-mediated endosome-to-plasma membrane sorting of transmembrane proteins.
Laboratory of Membrane Trafficking Mechanisms, Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Aobayama, Aoba-ku, Sendai, Miyagi, 980-8578, Japan.
Mitsunori
M
Fukuda
D000818:Animals; D003712:Dendrites / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008024:Ligands; D008544:Melanocytes / Q000378:metabolism; D020460:Melanosomes / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D000071446:Neuronal Outgrowth / Q000502:physiology; D009928:Organ Specificity; D011485:Protein Binding; D021381:Protein Transport; D050683:R-SNARE Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
C529611:ANKRD27 protein, human; D020662:Guanine Nucleotide Exchange Factors; D008024:Ligands; D008565:Membrane Proteins; D050683:R-SNARE Proteins; C121241:VAMP7 protein, human; D020691:rab GTP-Binding Proteins
Rab effector; SNARE; VPS9 domain; endosome; guanine nucleotide exchange factor; melanosome; membrane traffic; retromer; small GTPase Rab