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SDPR induces membrane curvature and functions in the formation of caveolae

Nature Cell Biology volume 11, pages 807–814 (2009)Cite this article

Abstract

Caveolae are plasma membrane invaginations with a characteristic flask-shaped morphology. They function in diverse cellular processes, including endocytosis. The mechanism by which caveolae are generated is not fully understood, but both caveolin proteins and PTRF (polymerase I and transcript release factor, also known as cavin) are important. Here we show that loss of SDPR (serum deprivation protein response) causes loss of caveolae. SDPR binds directly to PTRF and recruits PTRF to caveolar membranes. Overexpression of SDPR, unlike PTRF, induces deformation of caveolae and extensive tubulation of the plasma membrane. The B-subunit of Shiga toxin (STB) also induces membrane tubulation and these membrane tubes also originate from caveolae. STB colocalizes extensively with both SDPR and caveolin 1. Loss of caveolae reduces the propensity of STB to induce membrane tubulation. We conclude that SDPR is a membrane-curvature-inducing component of caveolae, and that STB-induced membrane tubulation is facilitated by caveolae.

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Figure 1: SDPR is a caveolar protein, but forms tubes at high expression levels.
Figure 2: SDPR is present in protein complexes with PTRF and caveolin 1 and can bind directly to PTRF in vitro.
Figure 3: SDPR is required for the formation of caveolar membrane invaginations, and induces formation of elongated caveolae when overexpressed.
Figure 4: SDPR recruits PTRF to caveolae and the plasma membrane.
Figure 5: SDPR overexpression induces membrane tubes derived from caveolae.
Figure 6: Membrane tubes induced by STB colocalize with SDPR and caveolin 1.
Figure 7: STB-induced membrane tubes grow from caveolae, and their formation is facilitated by caveolar proteins.

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Acknowledgements

We thank K. Riento, H. Pelham and S. Munro for comments on the manuscript. C.G.H. is supported by the MRC, Cowi Foundation, Ulla og Mogens Andersens Fond, Oticon Fonden, Julie Von Mullens Fond, Fuhrmann-Fonden, Krista og Viggo Petersen's Fond, Reinholdt W Jorck og Hustrus Fond, Christian og Ottilia Brorsons Rejselegat for Yngre Videnskabsmœnd- og Kvinder, Niels Bohr Fond and Henry Shaw's Legat. N.A.B. is supported by the MRC.

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Authors and Affiliations

  1. MRC-LMB, Hills Road, Cambridge, CB2 0QH, UK

    Carsten G. Hansen, Gillian Howard & Benjamin J. Nichols

  2. University of Cambridge, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0XY, UK

    Nicholas A. Bright

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  1. Carsten G. Hansen
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C.G.H. carried out the majority of experiments and data analysis, and participated in project planning; N.A.B. carried out cryo-electron microscopy; G.H. carried out all other electron microscopy and B.J.N. carried out some experiments and data analysis, participated in project planning, and wrote the paper.

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Correspondence to Benjamin J. Nichols.

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Hansen, C., Bright, N., Howard, G. et al. SDPR induces membrane curvature and functions in the formation of caveolae. Nat Cell Biol 11, 807–814 (2009). https://doi.org/10.1038/ncb1887

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