Mutational analysis of caveolin-induced vesicle formation. Expression of caveolin-1 recruits caveolin-2 to caveolae membranes

Shengwen Li, Ferruccio Galbiati, Daniela Volonte', Massimo Sargiacomo, Jeffrey A. Engelman, Kallol Das, Philipp E. Scherer, Michael P. Lisanti

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

Caveolae are vesicular organelles with a characteristic uniform diameter in the range of 50-100 nm. Although recombinant expression of caveolin-1 is sufficient to drive caveolae formation, it remains unknown what controls the uniform diameter of these organelles. One hypothesis is that specific caveolin-caveolin interactions regulate the size of caveolae, as caveolin-1 undergoes two stages of self-oligomerization. To test this hypothesis directly, we have created two caveolin-1 deletion mutants that lack regions of caveolin-1 that are involved in directing the self-assembly of caveolin-1 oligomers. More specifically, Cav-1 Δ61-100 lacks a region of the N-terminal domain that directs the formation of high molecular mass caveolin-1 homo-oligomers, while Cav-1 ΔC lacks a complete C-terminal domain that is required to allow caveolin homo-oligomers to interact with each other, forming a caveolin network. It is important to note that these two mutants retain an intact transmembrane domain. Our current results show that although Cav-1 Δ61-100 and Cav-1 ΔC are competent to drive vesicle formation, these vesicles vary widely in their size and shape with diameters up to 500-1000 nm. In addition, caveolin-induced vesicle formation appears to be isoform-specific. Recombinant expression of caveolin-2 under the same conditions failed to drive the formation of vesicles, while caveolin-3 expression yielded caveolae-sized vesicles. These results are consistent with the previous observation that in transformed NIH 3T3 cells that lack caveolin-1 expression, but continue to express caveolin-2, no morphologically distinguishable caveolae are observed. In addition, as caveolin-2 alone exists mainly as a monomer or homo-dimer, while caveolins 1 and 3 exist as high molecular mass homo-oligomers, our results are consistent with the idea that the formation of high molecular mass oligomers of caveolin are required to regulate the formation of uniform caveolae-sized vesicles. In direct support of this notion, regulated induction of caveolin-1 expression in transformed NIH 3T3 cells was sufficient to recruit caveolin-2 to caveolae membranes. The ability of caveolin-1 to recruit caveolin-2 most likely occurs through a direct interaction between caveolins 1 and 2, as caveolins 1 and 2 are normally co-expressed and interact with each other to form high molecular mass hetero-oligomers containing both caveolins 1 and 2. Copyright (C) 1998 Federation of European Biochemical Societies.

Original languageEnglish (US)
Pages (from-to)127-134
Number of pages8
JournalFEBS Letters
Volume434
Issue number1-2
DOIs
StatePublished - Aug 28 1998

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Caveolin 2
Caveolins
Caveolin 1
Caveolae
Membranes
Oligomers
Molecular mass
Caveolin 3
NIH 3T3 Cells
Organelles
Oligomerization

Keywords

  • Caveolae
  • Caveolin
  • Vesicle formation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Li, S., Galbiati, F., Volonte', D., Sargiacomo, M., Engelman, J. A., Das, K., ... Lisanti, M. P. (1998). Mutational analysis of caveolin-induced vesicle formation. Expression of caveolin-1 recruits caveolin-2 to caveolae membranes. FEBS Letters, 434(1-2), 127-134. https://doi.org/10.1016/S0014-5793(98)00945-4

Mutational analysis of caveolin-induced vesicle formation. Expression of caveolin-1 recruits caveolin-2 to caveolae membranes. / Li, Shengwen; Galbiati, Ferruccio; Volonte', Daniela; Sargiacomo, Massimo; Engelman, Jeffrey A.; Das, Kallol; Scherer, Philipp E.; Lisanti, Michael P.

In: FEBS Letters, Vol. 434, No. 1-2, 28.08.1998, p. 127-134.

Research output: Contribution to journalArticle

Li, Shengwen ; Galbiati, Ferruccio ; Volonte', Daniela ; Sargiacomo, Massimo ; Engelman, Jeffrey A. ; Das, Kallol ; Scherer, Philipp E. ; Lisanti, Michael P. / Mutational analysis of caveolin-induced vesicle formation. Expression of caveolin-1 recruits caveolin-2 to caveolae membranes. In: FEBS Letters. 1998 ; Vol. 434, No. 1-2. pp. 127-134.
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