Association of Src-family protein tyrosine kinases with sphingolipids in rat cerebellar granule cells differentiated in culture

Alessandro Prinetti, Nadia Marano, Simona Prioni, Vanna Chigorno, Laura Mauri, Riccardo Casellato, Guido Tettamanti, Sandro Sonnino

Research output: Contribution to journalArticlepeer-review

Abstract

Src family kinases play a relevant role in the development and differentiation of neuronal cells. They are abundant in sphingolipid-enriched membrane domains of many cell types, and these domains are hypothesized to function in bringing together molecules important to signal transduction. We studied the association of Src family tyrosine kinases and their negative regulatory kinase, Csk, with sphingolipids in sphingolipid-enriched domains of rat cerebellar granule cells differentiated in culture. We find that c-Src, Lyn and Csk are enriched in the sphingolipid-enriched fraction prepared from these cells. Coimmunoprecipitation experiments show that these and sphingolipids are part of the same domain. Cross-linking experiments with a photoactivable, radioactive GD1b derivative show that c-Src and Lyn, which are anchored to the membrane via a myristoyl chain, associate directly with GD1b. Csk, which is not inserted in the hydrophobic core of the membrane, is not photolabeled by this ganglioside. These results suggest that lipid-lipid, lipidprotein, and protein-protein interactions cooperate to maintain domain structure. We hypothesize that such interactions might play a role in the process of neuronal differentiation.

Original languageEnglish
Pages (from-to)223-232
Number of pages10
JournalGlycoconjugate Journal
Volume17
Issue number3-4
DOIs
Publication statusPublished - 2000

Keywords

  • Ganglioside enriched domains
  • Gangliosides
  • Neuronal cell cultures
  • Non-receptor tyrosine kinases
  • Sphingolipids
  • Src family proteins

ASJC Scopus subject areas

  • Biochemistry

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