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Endosomal sorting of VAMP3 is regulated by Phosphatidylinositol 4‐kinase IIa
Author(s) -
Jovic Marko,
Kean Michelle,
Gingras AnneClaude,
Brill Julie,
Balla Tamas
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1017.6
Subject(s) - microbiology and biotechnology , endosome , biology , endocytic cycle , exocytosis , vacuolar protein sorting , transmembrane protein , lipid bilayer fusion , endocytosis , biochemistry , receptor , membrane , intracellular
Membrane fusion along endocytic pathways is directly dependent on proper distribution of Soluble NSF‐attachment receptors (SNAREs). Although SNAREs are fairly promiscuous in vitro , significant specificity is achieved in vivo through spatial segregation and shielding of SNAREs prior to cognate Q‐SNARE binding. In particular, long R‐SNAREs are capable of autoinhibition, while short R‐SNAREs were shown to associate with phospholipids on vesicular membranes in vitro . However the exact regulation of this process and the potential lipid binding preference in vivo remains elusive. Here we have identified PtdIns4 P kinase PI4KIIa as a binding partner of VAMP3, a small recycling R‐SNARE. PI4KIIa depletion resulted in accumulation of VAMP3 on endosomal compartments, inhibited VAMP3 trafficking to perinuclear membranes and reduced the rate of VAMP3‐mediated transferrin recycling. Similarly, acute depletion of PtdIns4 P on endosomes significantly impaired VAMP3 sorting. In addition, VAMP3 association with its cognate Q‐SNARE Vti1a decreased upon PI4KIIa depletion. Taken together, these findings reveal a role for phospholipids in small R‐SNARE sorting, corroborating previous in vitro findings. Direct interaction with the lipid kinase PI4KIIa can, therefore, guarantee a localized supply of PtdIns4P to support the lipid requirement of endosomal SNARE function. Supported by the NICHD Intramural program