Insights into cargo sorting by SNX32 and its role in neurite outgrowth
- Indian Institute of Science Education and Research, Bhopal, India
- Institute Curie, France
- Indian Institute of Science Bangalore, India
- Stanford University, United States
- Indian Institute of Science Education and Research Pune, India
- Amala Cancer Research Centre, India
Abstract
Sorting nexins (SNX) are a family of proteins containing the Phox homology domain, which shows a preferential endo-membrane association and regulates cargo sorting processes. Here, we established that SNX32, a SNX-BAR (Bin/Amphiphysin/Rvs) sub-family member associates with SNX4 via its BAR domain and the residues A226, Q259, E256, R366 of SNX32, and Y258, S448 of SNX4 that lie at the interface of these two SNX proteins mediates this association. SNX32, via its PX domain, interacts with the Transferrin receptor (TfR) and Cation Independent Mannose-6-Phosphate Receptor (CIMPR), and the conserved F131 in its PX domain is important in stabilizing these interactions. Silencing of SNX32 leads to a defect in intracellular trafficking of TfR and CIMPR. Further, using SILAC-based differential proteomics of the wild type and the mutant SNX32, impaired in cargo binding, we identified Basigin (BSG), an immunoglobulin superfamily member, as a potential interactor of SNX32 in SHSY5Y cells. We then demonstrated that SNX32 binds to BSG through its PX domain and facilitates its trafficking to the cell surface. In Neuro-Glial cell lines, silencing of SNX32 leads to defects in neuronal differentiation. Moreover, abrogation in lactate transport in the SNX32 depleted cells led us to propose that SNX32 may contribute to maintaining the neuro-glial coordination via its role in BSG trafficking and the associated Monocarboxylate transporter activity. Taken together, our study showed that SNX32 mediates the trafficking of specific cargo molecules along distinct pathways.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting file; Source Data files have been provided separately.
Article and author information
Author details
Funding
Science and Engineering Research Board (CRG/2019/004580)
- Sunando Datta
Department of Biotechnology, Ministry of Science and Technology, India (DBT-JRF)
- Jini Sugatha
Indian Institute of Science (Apr2019/709/BS/iiserb/Sunando Datta)
- Sunando Datta
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2023, Sugatha et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 1,594
- views
-
- 245
- downloads
-
- 13
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Insights into cargo sorting by SNX32 and its role in neurite outgrowth
eLife 12:e84396.
https://doi.org/10.7554/eLife.84396
