Abstract
Expression of caveolin-1 and -3 in mouse smooth muscle cells in vivo was examined by immunohistochemistry. Caveolin-1 was detected in almost all smooth muscles examined, except for the pupillary dilator muscle, whereas caveolin-3 was present only in smooth muscles of some specific tissues. In the eye, the pupillary sphincter muscle was intensely positive for caveolin-3, whereas the ciliary muscle and pupillary dilator muscle were negative. In the gastrointestinal tract, caveolin-3 was detected in the inner circular layer, but not in the outer longitudinal layer. Vascular smooth muscle cells of the resistance-sized artery in the uterus and corpus cavernosum were intensely positive for caveolin-3, whereas those of the aorta were only weakly positive and those of the vena cava were negative. Caveolin-3 was also detected in smooth muscle cells of the urinary bladder, ureter, prostatic vas deferens, and seminal vesicle. The different levels of caveolin-3 expression among various smooth muscle tissues were confirmed by Western blot analysis. Even within the same muscle, the relative expression levels of caveolin-1 and -3 were variable among neighboring cells, suggesting distinct fine regulation of expression of these two caveolins. Moreover, even in the same cell, caveolin-1 and -3 showed different distributions. These results indicate that the two caveolins form distinct caveolae in smooth muscles, and that caveolin-1 and -3 serve different functions. Their differential expression may therefore be related to the functional diversity of smooth muscles.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Anderson RGW (1998) The caveolae membrane system. Annu Rev Biochem 67:199–225
Bozler E (1948) Conduction, automaticity, and tonus of visceral muscle. Experientia 4:213–218
Burnstock G (1970) Structure of smooth muscle and its innervation. In: Tomita T (ed) Smooth muscle. Arnold, London, pp 1–69
Capozza F, Cohen AW, Cheung MW, Sotgia F, Schubert W, Battista M, Lee H, Frank PG, Lisanti MP (2005) Muscle-specific interaction of caveolin isoforms: differential complex formation between caveolins in fibroblastic vs. muscle cells. Am J Physiol Cell Physiol 288:C677–C691
Couet J, Sargiacomo M, Lisanti MP (1997) Interaction of a receptor tyrosine kinase, EGF-R, with caveolins. Caveolin binding negatively regulates tyrosine and serine/threonine kinase activities. J Biol Chem 272:30429–30438
Das K, Lewis RY, Scherer PE, Lisanti MP (1999) The membrane-spanning domains of caveolins-1 and -2 mediate the formation of caveolin hetero-oligomers. Implications for the assembly of caveolae membranes in vivo. J Biol Chem 274:18721–18728
Deurs B van, Roepstorff K, Hommelgaard AM, Sandvig K (2003) Caveolae: anchored, multifunctional platforms in the lipid ocean. Trends Cell Biol 13:92–100
Doyle DD, Upshaw-Earley J, Bell E, Palfrey HC (2003) Expression of caveolin-3 in rat aortic vascular smooth muscle cells is determined by developmental state. Biochem Biophys Res Commun 304:22–25
Drab M, Verkade P, Elger M, Kasper M, Lohn M, Lauterbach B, Menne J, Lindschau C, Mende F, Luft FC, Schedl A, Haller H, Kurzchalia TV (2001) Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene-disrupted mice. Science 293:2449–2452
Fra AM, Williamson E, Simons K, Parton RG (1995) De novo formation of caveolae in lymphocytes by expression of VIP21-caveolin. Proc Natl Acad Sci USA 92:8655–8659
Fujimoto T, Hagiwara H, Aoki T, Kogo H, Nomura R (1998) Caveolae: from a morphological point of view. J Electron Microsc Tokyo 47:451–460
Fujimoto T, Kogo H, Nomura R, Une T (2000) Isoforms of caveolin-1 and caveolar structure. J Cell Sci 113:3509–3517
Galbiati F, Volont D, Minetti C, Chu JB, Lisanti MP (1999) Phenotypic behavior of caveolin-3 mutations that cause autosomal dominant limb girdle muscular dystrophy (LGMD-1C). Retention of lgmd-1c caveolin-3 mutants within the Golgi complex. J Biol Chem 274:25632–25641
Garcia-Cardena G, Martasek P, Masters BS, Skidd PM, Couet J, Li S, Lisanti MP, Sessa WC (1997) Dissecting the interaction between nitric oxide synthase (NOS) and caveolin. Functional significance of the NOS caveolin binding domain in vivo. J Biol Chem 272:25437–25440
Hagiwara Y, Nishina Y, Yorifuji H, Kikuchi T (2002) Immunolocalization of caveolin-1 and caveolin-3 in monkey skeletal, cardiac and uterine smooth muscles. Cell Struct Funct 27:375–382
Hasegawa K, Arakawa E, Oda S, Yanai N, Obinata M, Matsuda Y (1997) Novel smooth muscle cell lines from transgenic mice harboring temperature-sensitive SV40 large T-antigen gene. Temperature-dependent expression of smooth muscle myosin heavy chain-1 and calponin genes. J Mol Cell Cardiol 29:2177–2186
Knight D, D’Arbe M, Liang S, Phillips WD, Lavidis NA (2003) Regional differences in sympathetic purinergic transmission along the length of the mouse vas deferens. Synapse 47:225–235
Li S, Galbiati F, Volonte D, Sargiacomo M, Engelman JA, Das K, Scherer PE, Lisanti MP (1998) Mutational analysis of caveolin-induced vesicle formation. Expression of caveolin-1 recruits caveolin-2 to caveolae membranes. FEBS Lett 434:127–134
Li WP, Liu P, Pilcher BK, Anderson RGW (2001) Cell-specific targeting of caveolin-1 to caveolae, secretory vesicles, cytoplasm or mitochondria. J Cell Sci 114:1397–1408
van Meer G (2001) Caveolin, cholesterol, and lipid droplets? J Cell Biol 152:F29–34
Park DS, Woodman SE, Schubert W, Cohen AW, Frank PG, Chandra M, Shirani J, Razani B, Tang B, Jelicks LA, Factor SM, Weiss LM, Tanowitz HB, Lisanti MP (2002) Caveolin-1/3 double-knockout mice are viable, but lack both muscle and non-muscle caveolae, and develop a severe cardiomyopathic phenotype. Am J Pathol 160:2207–2217
Razani B, Engelman JA, Wang XB, Schubert W, Zhang XL, Marks CB, Macaluso F, Russell RG, Li M, Pestell RG, Di Vizio D, Hou H Jr, Knietz B, Lagaud G, Christ GJ, Edelmann W, Lisanti MP (2001) Caveolin-1 null mice are viable, but show evidence of hyper-proliferative and vascular abnormalities. J Biol Chem 276:38121–38138
Razani B, Lisanti MP (2001a) Caveolin-deficient mice: insights into caveolar function human disease. J Clin Invest 108:1553–1561
Razani B, Lisanti MP (2001b) Caveolins and caveolae: molecular and functional relationships. Exp Cell Res 271:36–44
Rothberg KG, Heuser JE, Donzell WC, Ying YS, Glenney JR, Anderson RGW (1992) Caveolin, a protein component of caveolae membrane coats. Cell 68:673–682
Rybin VO, Grabham PW, Elouardighi H, Steinberg SF (2003) Caveolae-associated proteins in cardiomyocytes: caveolin-2 expression and interactions with caveolin-3. Am J Physiol Heart Circ Physiol 285:H325–H332
Scherer PE, Okamoto T, Chun M, Nishimoto I, Lodish HF, Lisanti MP (1996) Identification, sequence, and expression of caveolin-2 defines a caveolin gene family. Proc Natl Acad Sci USA 93:131–135
Segal SS, Brett SE, Sessa WC (1999) Codistribution of NOS and caveolin throughout peripheral vasculature and skeletal muscle of hamsters. Am J Physiol 277:H1167–H1177
Song KS, Scherer PE, Tang Z, Okamoto T, Li S, Chafel M, Chu C, Kohtz DS, Lisanti MP (1996) Expression of caveolin-3 in skeletal, cardiac, and smooth muscle cells. Caveolin-3 is a component of the sarcolemma and co-fractionates with dystrophin and dystrophin-associated glycoproteins. J Biol Chem 271:15160–15165
Sotgia F, Bonuccelli G, Minetti C, Woodman SE, Capozza F, Kemp RG, Scherer PE, Lisanti MP (2003) Phosphofructokinase muscle-specific isoform requires caveolin-3 expression for plasma membrane recruitment and caveolar targeting: implications for the pathogenesis of caveolin-related muscle diseases. Am J Pathol 163:2619–2634
Sotgia F, Lee JK, Das K, Bedford M, Petrucci TC, Macioce P, Sargiacomo M, Minetti C, Sudol M, Lisanti MP (2000) Caveolin-3 directly interacts with the C-terminal tail of beta-dystroglycan: identification of a central WW-like domain within caveolin family members. J Biol Chem 275:38048–38058
Tang Z, Scherer PE, Okamoto T, Song K, Chu C, Kohtz DS, Nishimoto I, Lodish HF, Lisanti MP (1996) Molecular cloning of caveolin-3, a novel member of the caveolin gene family expressed predominantly in muscle. J Biol Chem 271:2255–2261
Toya Y, Schwencke C, Couet J, Lisanti MP, Ishikawa Y (1998) Inhibition of adenylyl cyclase by caveolin peptides. Endocrinology 139:2025–2031
Venema VJ, Ju H, Zou R, Venema RC (1997) Interaction of neuronal nitric-oxide synthase with caveolin-3 in skeletal muscle. Identification of a novel caveolin scaffolding/inhibitory domain. J Biol Chem 272:28187–28190
Way M, Parton RG (1996) M-caveolin, a muscle-specific caveolin-related protein. FEBS Lett 378:108–112
Woodman SE, Cheung MW, Tarr M, North AC, Schubert W, Lagaud G, Marks CB, Russell RG, Hassan GS, Factor SM, Christ GJ, Lisanti MP (2004a) Urogenital alterations in aged male caveolin-1 knockout mice. J Urol 171:950–957
Woodman SE, Sotgia F, Galbiati F, Minetti C, Lisanti MP (2004b) Caveolinopathies: mutations in caveolin-3 cause four distinct autosomal dominant muscle diseases. Neurology 62:538–543
Yamamoto M, Toya Y, Schwencke C, Lisanti MP, Myers MG Jr, Ishikawa Y (1998) Caveolin is an activator of insulin receptor signaling. J Biol Chem 273:26962–26968
Acknowledgements
We are grateful to Dr. Akiko Iizuka-Kogo and Dr. Ryuji Nomura, Fujita Health University School of Medicine, and to Dr. Shigeko Torihashi, Nagoya University Graduate School of Medicine, for their helpful discussions.
Author information
Authors and Affiliations
Corresponding author
Additional information
This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of the Japanese Government.
Rights and permissions
About this article
Cite this article
Kogo, H., Ito, Sy., Moritoki, Y. et al. Differential expression of caveolin-3 in mouse smooth muscle cells in vivo. Cell Tissue Res 324, 291–300 (2006). https://doi.org/10.1007/s00441-005-0130-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00441-005-0130-z