Anti-SNX7 (full length) polyclonal antibody

The sorting nexins (SNXs) are a family of peripheral membrane proteins that direct protein trafficking decisions within the endocytic network. Emerging evidence in yeast and mammalian cells implicates a subgroup of SNXs in selective and non-selective forms of autophagy. Using siRNA and CRISPR-Cas9, we demonstrate that the SNX-BAR protein SNX4 is needed for efficient LC3 (also known as MAP1LC3) lipidation and autophagosome assembly in mammalian cells. SNX-BARs exist as homo- and hetero-dimers, and we show that SNX4 forms functional heterodimers with either SNX7 or SNX30 that associate with tubulovesicular endocytic membranes. Detailed image-based analysis during the early stages of autophagosome assembly reveals that SNX4-SNX7 is an autophagy-specific SNX-BAR heterodimer, required for efficient recruitment and/or retention of core autophagy regulators at the nascent isolation membrane. SNX4 partially colocalises with juxtanuclear ATG9A-positive membranes, with our data linking the autophagy defect upon SNX4 disruption to the mis-trafficking and/or retention of ATG9A in the Golgi region. Taken together, our findings show that the SNX4-SNX7 heterodimer coordinates ATG9A trafficking within the endocytic network to establish productive autophagosome assembly sites, thus extending knowledge of SNXs as positive regulators of autophagy.

Abnormal production of amyloid-beta peptides (A beta) by proteolytic processing of amyloid precursor protein (APP) is thought to be central to the pathogenesis of Alzheimer's disease (AD). Although many efforts have been made to investigate mechanisms that regulate APP processing, many details remain incompletely understood. Sorting nexins (SNXs) are a family of proteins which are involved in many intracellular trafficking events. Several SNXs have been implicated in APP processing and A beta production. In this study, we extended the investigation to SNX7. We found that overexpression of SNX7 in HEK293T cells reduces the levels of secreted A beta and beta-cleaved N-terminal APP fragments (sAPP beta). Moreover, SNX7 overexpression caused a significant reduction of the steady-state levels of APP as well as of the cell surface APP levels. By using NH4CI and Bafilomycin A1 to inhibit the lysosomal degradative pathway, we found that the reduction of APP induced by SNX7 overexpression was prevented by such inhibition. No change in the cell surface distribution or steady-state levels of BACE1 was detected after overexpression of SNX7. Taken together, these results suggest that SNX7 regulates A beta production by directing APP for degradation. (C) 2017 Elsevier Inc. All rights reserved.