DIPK2A Promotes STX17- and VAMP7-mediated Autophagosome-lysosome Fusion by Binding to VAMP7B.

DIPK2A Promotes STX17- and VAMP7-mediated Autophagosome-lysosome Fusion by Binding to VAMP7B.
Autophagy. 2019 Jun 28;:
Authors: Tian X, Zheng P, Zhou C, Wang X, Ma H, Ma W, Zhou X, Teng J, Chen J
Abstract
Autophagosome and lysosome fusion is an important macroautophagy/autophagy process for cargo degradation, and SNARE proteins, including STX17, SNAP29, VAMP7 and VAMP8, are key players in this process. However, the manner in which this process is precisely regulated is poorly understood. Here, we show that VAMP7B, a SNARE domain-disrupted isoform of R-SNARE protein VAMP7, competes with SNARE domain functional isoform VAMP7A to bind to STX17 and inhibits autophagosome-lysosome fusion. Moreover, we show that DIPK2A, a late endosome- and lysosome-localized protein, binds to VAMP7B, which inhibits the interaction of VAMP7B with STX17 and enhances the binding of STX17 to VAMP7A, thus enhancing autophagosome-lysosome fusion. Furthermore, DIPK2A participates in autophagic degradation of mitochondria proteins and alleviates apoptosis. Thus, we reveal a new aspect of autophagosome-lysosome fusion in which different isoforms of VAMP7 compete with STX17 and their regulation by DIPK2A.
PMID: 31251111 [PubMed - as supplied by publisher]

Source: Autophagy - June 27, 2019 Category: Cytology Authors: Tian X, Zheng P, Zhou C, Wang X, Ma H, Ma W, Zhou X, Teng J, Chen J Tags: Autophagy Source Type: research