Role of the Ste20-like kinase SLK in podocyte adhesion

Andrey V Cybulsky1, Joan Papillon1, Craig Bryan1

  • 1Department of Medicine, McGill University Health Centre Research Institute, McGill University, Montreal, Quebec, Canada.

Physiological Reports
|January 1, 2024
PubMed

Insights

Sphingolipid long-chain base kinase (SLK) regulates cell adhesion. While SLK deletion worsens kidney podocyte injury and alters cell adhesion, key adhesion proteins are not its major substrates.

Area of Science:

  • Cell Biology
  • Nephrology
  • Molecular Biology

Background:

  • Sphingolipid long-chain base kinase (SLK) is crucial for regulating the cytoskeleton, cell adhesion, and migration.
  • Podocyte-specific SLK deletion in mice results in age-related podocyte injury and exacerbates focal segment glomerulosclerosis (FSGS) in adriamycin nephrosis models.

Purpose of the Study:

  • To investigate whether adhesion proteins are substrates of SLK.
  • To elucidate the role of SLK in podocyte adhesion and focal adhesion complex (FAC) regulation in health and disease.

Main Methods:

  • Analysis of a protein kinase phosphorylation site dataset to identify potential SLK substrates.
  • Experimental manipulation of SLK in cultured podocytes and in mice with adriamycin-induced nephrosis.
  • Assessment of cell adhesion, focal adhesion complex composition, and protein phosphorylation (including focal adhesion kinase Y397).

Main Results:

  • SLK deletion in cultured podocytes increased adhesion to collagen and reduced FACs containing paxillin, vinculin, and talin-1, particularly in adriamycin-induced injury.
  • SLK showed a minor effect on paxillin S250 phosphorylation but did not phosphorylate talin-1.
  • SLK deletion did not alter glomerular expression of talin-1 and vinculin but modestly increased focal adhesion kinase phosphorylation in adriamycin nephrosis.

Conclusions:

  • SLK plays a role in decreasing podocyte adhesion.
  • Despite alterations in FACs, key adhesion proteins like paxillin, vinculin, and talin-1 are not major substrates of SLK in podocytes during health or adriamycin-induced injury.

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