Gangliosides and β1-integrin are required for caveolae and membrane domains

Raman Deep Singh, David L. Marks, Eileen L. Holicky, Christine L. Wheatley, Tatiana Kaptzan, Satoshi B. Sato, Toshihide Kobayashi, Kun Ling, Richard E. Pagano

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Caveolae are plasma membrane domains involved in the uptake of certain pathogens and toxins. Internalization of some cell surface integrins occurs via caveolae suggesting caveolae may play a crucial role in modulating integrin-mediated adhesion and cell migration. Here we demonstrate a critical role for gangliosides (sialo-glycosphingolipids) in regulating caveolar endocytosis in human skin fibroblasts. Pretreatment of cells with endoglycoceramidase (cleaves glycosphingolipids) or sialidase (modifies cell surface gangliosides and glycoproteins) selectively inhibited caveolar endocytosis by >70%, inhibited the formation of plasma membrane domains enriched in sphingolipids and cholesterol ('lipid rafts'), reduced caveolae and caveolin-1 at the plasma membrane by approximately 80%, and blunted activation of β1-integrin, a protein required for caveolar endocytosis in these cells. These effects could be reversed by a brief incubation with gangliosides (but not with asialo-gangliosides or other sphingolipids) at 10°C, suggesting that sialo-lipids are critical in supporting caveolar endocytosis. Endoglycoceramidase treatment also caused a redistribution of focal adhesion kinase, paxillin, talin, and PIP Kinase Iγ away from focal adhesions. The effects of sialidase or endoglycoceramidase on membrane domains and the distribution of caveolin-1 could be recapitulated by β1-integrin knockdown. These results suggest that both gangliosides and β1-integrin are required for maintenance of caveolae and plasma membrane domains.

Original languageEnglish (US)
Pages (from-to)348-360
Number of pages13
JournalTraffic
Volume11
Issue number3
DOIs
StatePublished - Mar 2010

Fingerprint

endoglycoceramidase
Caveolae
Gangliosides
Integrins
Cell membranes
Endocytosis
Membranes
Cell Membrane
Caveolin 1
Glycosphingolipids
Sphingolipids
Neuraminidase
Adhesion
Talin
Membrane Microdomains
Paxillin
Lipids
Focal Adhesion Protein-Tyrosine Kinases
Focal Adhesions
Membrane Glycoproteins

Keywords

  • Caveolar endocytosis
  • Caveolin-1
  • Endoglycoceramidase
  • Focal adhesions
  • Glycosphingolipids
  • Sialidase

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Structural Biology
  • Molecular Biology
  • Genetics
  • Medicine(all)

Cite this

Singh, R. D., Marks, D. L., Holicky, E. L., Wheatley, C. L., Kaptzan, T., Sato, S. B., ... Pagano, R. E. (2010). Gangliosides and β1-integrin are required for caveolae and membrane domains. Traffic, 11(3), 348-360. https://doi.org/10.1111/j.1600-0854.2009.01022.x

Gangliosides and β1-integrin are required for caveolae and membrane domains. / Singh, Raman Deep; Marks, David L.; Holicky, Eileen L.; Wheatley, Christine L.; Kaptzan, Tatiana; Sato, Satoshi B.; Kobayashi, Toshihide; Ling, Kun; Pagano, Richard E.

In: Traffic, Vol. 11, No. 3, 03.2010, p. 348-360.

Research output: Contribution to journalArticle

Singh, RD, Marks, DL, Holicky, EL, Wheatley, CL, Kaptzan, T, Sato, SB, Kobayashi, T, Ling, K & Pagano, RE 2010, 'Gangliosides and β1-integrin are required for caveolae and membrane domains', Traffic, vol. 11, no. 3, pp. 348-360. https://doi.org/10.1111/j.1600-0854.2009.01022.x
Singh RD, Marks DL, Holicky EL, Wheatley CL, Kaptzan T, Sato SB et al. Gangliosides and β1-integrin are required for caveolae and membrane domains. Traffic. 2010 Mar;11(3):348-360. https://doi.org/10.1111/j.1600-0854.2009.01022.x
Singh, Raman Deep ; Marks, David L. ; Holicky, Eileen L. ; Wheatley, Christine L. ; Kaptzan, Tatiana ; Sato, Satoshi B. ; Kobayashi, Toshihide ; Ling, Kun ; Pagano, Richard E. / Gangliosides and β1-integrin are required for caveolae and membrane domains. In: Traffic. 2010 ; Vol. 11, No. 3. pp. 348-360.
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