1. Cell Biology

Insights into cargo sorting by SNX32 and its role in neurite outgrowth

  1. Jini Sugatha  Is a corresponding author
  2. Amulya Priya
  3. Prateek Raj
  4. Ebsy Jaimon
  5. Uma Swaminathan
  6. Anju Jose
  7. Thomas John Pucadyil
  8. Sunando Datta  Is a corresponding author
  1. Indian Institute of Science Education and Research, Bhopal, India
  2. Institute Curie, France
  3. Indian Institute of Science Bangalore, India
  4. Stanford University, United States
  5. Indian Institute of Science Education and Research Pune, India
  6. Amala Cancer Research Centre, India
https://doi.org/10.7554/eLife.84396
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Cite this article
  1. Jini Sugatha
  2. Amulya Priya
  3. Prateek Raj
  4. Ebsy Jaimon
  5. Uma Swaminathan
  6. Anju Jose
  7. Thomas John Pucadyil
  8. Sunando Datta
(2023)
Insights into cargo sorting by SNX32 and its role in neurite outgrowth
eLife 12:e84396.
https://doi.org/10.7554/eLife.84396
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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

  1. Jini Sugatha

    Indian Institute of Science Education and Research, Bhopal, Bhopal, India
    For correspondence
    ssjini@outlook.com
    Competing interests
    The authors declare that no competing interests exist.

  2. Amulya Priya

    Research Centre, Institute Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.

  3. Prateek Raj

    Molecular Biophysics Unit, Indian Institute of Science Bangalore, Bangalore, India
    Competing interests
    The authors declare that no competing interests exist.

  4. Ebsy Jaimon

    Department of Biochemistry, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6845-2095

  5. Uma Swaminathan

    Indian Institute of Science Education and Research Pune, Pune, India
    Competing interests
    The authors declare that no competing interests exist.

  6. Anju Jose

    Amala Cancer Research Centre, Thrissur, India
    Competing interests
    The authors declare that no competing interests exist.

  7. Thomas John Pucadyil

    Indian Institute of Science Education and Research Pune, Pune, India
    Competing interests
    The authors declare that no competing interests exist.

  8. Sunando Datta

    Indian Institute of Science Education and Research, Bhopal, Bhopal, India
    For correspondence
    sunando@iiserb.ac.in
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1417-0276

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.

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  1. Jini Sugatha
  2. Amulya Priya
  3. Prateek Raj
  4. Ebsy Jaimon
  5. Uma Swaminathan
  6. Anju Jose
  7. Thomas John Pucadyil
  8. Sunando Datta
(2023)
Insights into cargo sorting by SNX32 and its role in neurite outgrowth
eLife 12:e84396.
https://doi.org/10.7554/eLife.84396

Share this article

https://doi.org/10.7554/eLife.84396

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