Abstract
Recycling endosomes maintain plasma membrane homeostasis and are important for cell polarity, migration, and cytokinesis. Yet, the molecular machineries that drive endocytic recycling remain largely unclear. The CORVET complex is a multi-subunit tether required for fusion between early endosomes. Here we show that the CORVET-specific subunits Vps3 and Vps8 also regulate vesicular transport from early to recycling endosomes. Vps3 and Vps8 localise to Rab4-positive recycling vesicles and co-localise with the CHEVI complex on Rab11-positive recycling endosomes. Depletion of Vps3 or Vps8 does not affect transferrin recycling, but delays the delivery of internalised integrins to recycling endosomes and their subsequent return to the plasma membrane. Consequently, Vps3/8 depletion results in defects in integrin-dependent cell adhesion and spreading, focal adhesion formation, and cell migration. These data reveal a role for Vps3 and Vps8 in a specialised recycling pathway important for integrin trafficking.
Highlights
Recycling endosomes maintain plasma membrane homeostasis and are important for cell polarity, migration, and cytokinesis
The hexameric core vacuole/ endosome tethering (CORVET) complex consists of a core (Vps[11], Vps[16], Vps[18] and Vps33A), which is shared with the late endosomal homotypic fusion and protein sorting (HOPS) tethering complex, and contains the two CORVET-specific subunits Vps[8] and Vps[39,12]
We show that Vps[3] and Vps[8] independent of CORVET are required for recycling of selected cargo proteins
Summary
Recycling endosomes maintain plasma membrane homeostasis and are important for cell polarity, migration, and cytokinesis. Vps3/8 depletion results in defects in integrin-dependent cell adhesion and spreading, focal adhesion formation, and cell migration These data reveal a role for Vps[3] and Vps[8] in a specialised recycling pathway important for integrin trafficking. EE-EE fusion is initiated by activation of Rab[5], which recruits multiple effector proteins, including the class C core vacuole/ endosome tethering (CORVET) complex[8,9,10,11]. To our surprise we found that the CORVET-specific Vps[3] and Vps[8] subunits interact directly with each other and localise to Rab4-positive recycling vesicles and CHEVI-positive REs. we show that Vps[3] and Vps[8] function in a specialised pathway required for integrin recycling, and thereby regulates integrin-dependent cell adhesion and migration
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