Structure-based reassessment of the caveolin signaling model: do caveolae regulate signaling through caveolin-protein interactions?
Caveolin proteins drive formation of caveolae, specialized cell-surface microdomains that influence cell signaling. Signaling proteins are proposed to use conserved caveolin-binding motifs (CBMs) to associate with caveolae via the caveolin scaffolding domain (CSD). However, structural and bioinformatic analyses argue against such direct physical interactions: in the majority of signaling proteins, the CBM is buried and inaccessible. Putative CBMs do not form a common structure for caveolin recognition, are not enriched among caveolin-binding proteins, and are even more common in yeast, which lack caveolae. We propose that CBM/CSD-dependent interactions are unlikely to mediate caveolar signaling, and the basis for signaling effects should therefore be reassessed.
The Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia. b.collins@imb.uq.edu.au
Brett M
BM
Collins
Melissa J
MJ
Davis
John F
JF
Hancock
Robert G
RG
Parton
D020816:Amino Acid Motifs / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D051242:Caveolin 1 / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D054730:Protein Interaction Domains and Motifs / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship
D051242:Caveolin 1