8.A.26 The Caveolin (Caveolin) Family

Caveolin-1 is the primary structural protein of caveolae, small plasma membrane invaginations that are involved in transcytosis, cholesterol transport, signal transduction and cancer (Quest et al., 2008). It regulates endothelial permeability and therefore controls transport of fluids and solutes across semi-permeable vascular endothelial barriers (Minshall and Malik, 2006; Sun et al., 2011). It regulated both the transcellular and paracellular pathways, and controls vesicle trafficking including localization of signalling molecules that mediate vesicle fission, endocytosis, fusion and exocytosis (Minshall and Malik, 2006). Cholesterol efflux from lipid-loaded cells is also regulated by calveolin-1 via a 'caveolae transport center', an intracellular trafficking system of the caveolin-1 complex, and transmembrane transport systems of the ABC-A1 (TC#3.A.1.211.1) and SR-B1 complexes. Both ABC transporters transfer cholesterol from caveolae to extracellular HDL/ApoA1 (Luo et al., 2010). A proline in the integral membrane reentrant helix of caveolin-1 controls the topology of the protein (Aoki et al., 2010).  Caveolins interact directly with several Kv1 channels such as Kv1.3 (1.A.1.2.4) to influence their activities and promote associations with lipid rafts (Pérez-Verdaguer et al. 2016).  Cav-1, Cav-2 and Cavin-1 may be reliable markers for identification of liposarcoma tumors characterized by consistent adipogenic differentiation (Codenotti et al. 2016).

Progesterone and its polar metabolites trigger meiotic division in the amphibian oocyte through a non-genomic signaling system at the plasma membrane. Site-directed mutagenesis studies of ouabain binding and progesterone-ouabain competition indicated that Progesterone binds to a 23 amino acid extracellular loop of the plasma membrane α-subunit of the Na/K-ATPase. Integral membrane proteins such as caveolins are reported to form Na/K-ATPase-peptide complexes essential for signal transduction. Morrill et al. (2012) characterized the progesterone-induced Na/K-ATPase-caveolin (CAV-1)-steroid 5α-reductase interactions initiating meiotic division. Peptide sequence analysis algorithms indicated that CAV-1 contains two plasma membrane spanning helices separated by as few as 1-2 amino acid residues at the cell surface. The CAV-1 scaffolding domain, reported to interact with CAV-1 binding (CB) motifs in signaling proteins, overlaps TMS1. The α-subunits of Na/K-ATPases (10 TMSs) contain double CB motifs within TMS1 and TMS10. Steroid 5α-reductase (6 TMSs), an initial step in polar steroid formation, contains CB motifs overlapping TMSs 1 and 6. Computer analyses predicted that interaction between antipathic strands may bring CB motifs and scaffolding domains into close proximity, initiating allostearic changes. Progesterone binding to the α-subunit may thus facilitate CB motif:CAV-1 interactions, which in turn induce helix-helix interaction and generate both a signaling cascade and formation of polar steroids.



This family belongs to the .

 

References:

Codenotti, S., M. Vezzoli, P.L. Poliani, M. Cominelli, F. Bono, H. Kabbout, F. Faggi, N. Chiarelli, M. Colombi, I. Zanella, G. Biasiotto, A. Montanelli, L. Caimi, E. Monti, and A. Fanzani. (2016). Caveolin-1, Caveolin-2 and Cavin-1 are strong predictors of adipogenic differentiation in human tumors and cell lines of liposarcoma. Eur J. Cell Biol. [Epub: Ahead of Print]

Li, X., F. Yao, W. Zhang, C. Cheng, B. Chu, Y. Liu, Y. Mei, Y. Wu, X. Zou, and L. Hou. (2014). Identification, expression pattern, cellular location and potential role of the caveolin-1 gene from Artemia sinica. Gene 540: 161-170.

Meshulam, T., J.R. Simard, J. Wharton, J.A. Hamilton, and P.F. Pilch. (2006). Role of caveolin-1 and cholesterol in transmembrane fatty acid movement. Biochemistry 45: 2882-2893.

Morrill GA., Kostellow AB. and Askari A. (2012). Caveolin-Na/K-ATPase interactions: role of transmembrane topology in non-genomic steroid signal transduction. Steroids. 77(11):1160-8.

Pérez-Verdaguer, M., J. Capera, R. Martínez-Mármol, M. Camps, N. Comes, M.M. Tamkun, and A. Felipe. (2016). Caveolin interaction governs Kv1.3 lipid raft targeting. Sci Rep 6: 22453.

Shin, J., Y.H. Jung, D.H. Cho, M. Park, K.E. Lee, Y. Yang, C. Jeong, B.H. Sung, J.H. Sohn, J.B. Park, and D.H. Kweon. (2015). Display of membrane proteins on the heterologous caveolae carved by caveolin-1 in the Escherichia coli cytoplasm. Enzyme Microb Technol 79-80: 55-62.

Udayantha, H.M.V., S.D.N.K. Bathige, T.T. Priyathilaka, S. Lee, M.J. Kim, and J. Lee. (2017). Identification and characterization of molluscan caveolin-1 ortholog from Haliotis discus discus: Possible involvement in embryogenesis and host defense mechanism against pathogenic stress. Gene Expr Patterns 27: 85-92. [Epub: Ahead of Print]

Examples:

TC#NameOrganismal TypeExample
8.A.26.1.1

Calveolin-1 of 178 aas and 2 TMSs.  Caveolae are membrane-budding structures in vertebrate cells, and calveolin-1 forms membrane curvature and endocytic vesicles. Caveolae-like structures can form in E. coli through the expression of caveolin-1.  These caveolae are ~100 nm in diameter and can harbor both animal and bacterial transmembrane proteins (Shin et al. 2015). Molecules from the outside can be taken up into these structures. Transport of fatty acids across the plasma membrane is modulated by caveolin-1 and cholesterol and is not dependent on the putative fatty acid transport proteins, CD36 and FATP (Meshulam et al. 2006).

Animals

Caveolin-1 of Homo sapiens (Q03135)

 
8.A.26.1.2

Caveolin-1 (219 aas)

Animals

Caveolin-1 of Xenopus laevis (Q8JHX1)

 
8.A.26.1.3

Caveolin-2 (160 aas)

Animals

Caveolin-2 of Xenopus laevis (Q8JHX0)

 
8.A.26.1.4

Caveolin-3 (141 aas)

Animals

Caveolin-3 of Xenopus laevis (Q8JHW9)

 
8.A.26.1.5

Caveolin-1 of 224 aas.  May act as a scaffolding protein within caveolar membranes. Interacts directly with G-protein alpha subunits and transport proteins, and can functionally regulate their activities (Li et al. 2014).

Animals

Caveolin-1 of Artemia sinica

 
8.A.26.1.6

Caveolin-1, CAV1, of 127 aas and 2 TMSs.  It plays a central role in signal transduction, substrate transport, and membrane trafficking in various cell types. CAV1 also plays an important rolein embryogenesis and host immune defense in disk abalone (Udayantha et al. 2017).

 

Caveolin-1 of Haliotis discus discus (the disc abalone)