Caveolae: From Cell Biology to Animal Physiology

Razani, Babak; Woodman, Scott E.; Lisanti, Michael P.

doi:10.1124/pr.54.3.431

Cited by 888 publications

(878 citation statements)

References 283 publications

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“…The direct interaction of these two complementary motifs has been confirmed in signaling proteins like G i2␣ protein and receptor tyrosine kinases (e.g. epidermal growth factor and insulin receptors) (24,27). Here, we report for the first time that hSlo1 and caveolin-1 interaction requires the consensus caveolin-1-binding motif 1007 YNMLCFGIY 1015 ( XXXX XX ) in hSlo1 as most (ϳ80%) of hSlo1-caveolin-1 association was lost following its deletion (Fig.…”

Section: Association Of Slo1 Protein With Caveolin-1 In Native Aorticmentioning

confidence: 67%

“…*, significantly different with respect to normalized WT constructs. 1007 YNMLCFGIY 1015 -Caveolin-1 not only serves as a scaffold to keep together signaling molecules in caveolae but may also have functional consequences on their interacting protein partners by modifying their traffic in caveolar vesicles and/or inhibiting enzymatic protein activity (23,24). Thus, we wondered whether caveolin-1 interaction with hSlo1 could affect hSlo1 surface expression and/or its voltagedependent activation.…”

Section: Co-localization Of Slo1 and Caveolin-1 In Freshly Dissociatementioning

confidence: 99%

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Slo1 Caveolin-binding Motif, a Mechanism of Caveolin-1-Slo1 Interaction Regulating Slo1 Surface Expression

Alioua¹,

Lü²,

Kumar³

et al. 2008

Journal of Biological Chemistry

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The large conductance, voltage-and Ca 2؉ -activated potassium (MaxiK, BK) channel and caveolin-1 play important roles in regulating vascular contractility. Here, we hypothesized that the MaxiK ␣-subunit (Slo1) and caveolin-1 may interact with each other. Slo1 and caveolin-1 physiological association in native vascular tissue is strongly supported by (i) detergent-free purification of caveolin-1-rich domains demonstrating a pool of aortic Slo1 co-migrating with caveolin-1 to light density sucrose fractions, (ii) reverse co-immunoprecipitation, and (iii) double immunolabeling of freshly isolated myocytes revealing caveolin-1 and Slo1 proximity at the plasmalemma. In HEK293T cells, Slo1-caveolin-1 association was unaffected by the smooth muscle MaxiK ␤1-subunit. Sequence analysis revealed two potential caveolin-binding motifs along the Slo1 C terminus, one equivalent, 1007 YNMLCFGIY 1015 , and another mirror image, 537 YT-EYLSSAF 545 , to the consensus sequence, XXXX XX . Deletion of 1007 YNMLCFGIY 1015 caused ϳ80% loss of Slo1-caveolin-1 association while preserving channel normal folding and overall Slo1 and caveolin-1 intracellular distribution patterns. 537 YTEYLSSAF 545 deletion had an insignificant dissociative effect. Interestingly, caveolin-1 coexpression reduced Slo1 surface and functional expression near 70% without affecting channel voltage sensitivity, and deletion of 1007 YNMLCF-GIY 1015 motif obliterated channel surface expression. The results suggest 1007 YNMLCFGIY 1015 possible participation in Slo1 plasmalemmal targeting and demonstrate its role as a main mechanism for caveolin-1 association with Slo1 potentially serving a dual role: (i) maintaining channels in intracellular compartments downsizing their surface expression and/or (ii) serving as anchor of plasma membrane resident channels to caveolin-1-rich membranes. Because the caveolin-1 scaffolding domain is juxtamembrane, it is tempting to suggest that Slo1-caveolin-1 interaction facilitates the tethering of the Slo1 C-terminal end to the membrane.Large conductance, voltage-and Ca 2ϩ -activated potassium (MaxiK, BK) 4 channels play important roles in vascular, neuronal, and urinary functions. In vascular smooth muscle, MaxiK channel appears to be a unique signaling protein because of its ability to mediate the effects of several vasoconstricting as well as vasodilating agents. The ability of MaxiK protein to complete with high fidelity these opposite tasks calls for specific associations and subcellular compartmentalization with corresponding signaling partners (1). Recently, it has been appreciated that many signaling molecules are segregated primarily in specialized microdomains like caveolae (plasma membrane invaginations enriched with cholesterol and caveolin protein), thereby, optimizing signal transduction between agonists and specific effectors (2).Three caveolin proteins have been identified, caveolin-1, -2, and -3. All of them seem to be expressed in smooth muscle (3, 4). However, gene ablation experiments have shown that caveolin-1 p...

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Section: Association Of Slo1 Protein With Caveolin-1 In Native Aorticmentioning

confidence: 67%

Section: Co-localization Of Slo1 and Caveolin-1 In Freshly Dissociatementioning

confidence: 99%

Slo1 Caveolin-binding Motif, a Mechanism of Caveolin-1-Slo1 Interaction Regulating Slo1 Surface Expression

Alioua¹,

Lü²,

Kumar³

et al. 2008

Journal of Biological Chemistry

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“…The best described examples are intracellular processes regulated by protein machines, such as the spliceosome, proteasome, or transcriptional and translational machinery (40). However, there is emerging evidence that analogous protein assemblies may occur on the cell surface, possibly in lipid microdomains (41)(42)(43). Although interactions between peptide receptors and related peptidases have not been extensively studied, recent evidence indicates that ACE and B2 kinin receptor do interact on the cell surface (44,45).…”

Section: Discussionmentioning

confidence: 99%

Carboxypeptidase M and Kinin B1 Receptors Interact to Facilitate Efficient B1 Signaling from B2 Agonists

Zhang

Tan

Zhang

et al. 2008

Journal of Biological Chemistry

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Kinin B1 receptor (B1R) expression is induced by injury or inflammatory mediators, and its signaling produces both beneficial and deleterious effects. Kinins cleaved from kininogen are agonists of the B2R and must be processed by a carboxypeptidase to generate B1R agonists des-Arg 9 -bradykinin or desArg 10 Carboxypeptidase M (CPM) 2 was discovered as a glycosylphosphatidylinositol (GPI)-anchored membrane protein with B-type carboxypeptidase activity (1-3) and is a member of the "regulatory" or carboxypeptidase N/E subfamily of metallocarboxypeptidases (4 -8) based on its cDNA sequence (9), genomic structure (10), and x-ray crystal structure (11). The overall structure of CPM is composed of a 295-residue N-terminal catalytic domain, followed by an 86-residue conical ␤-sandwich (transthyretin-like domain) and a unique 25-residue extension to which the GPI anchor is post-translationally attached (11).CPM cleaves only C-terminal Arg or Lys residues, and some of its endogenous substrates include bradykinin, anaphylatoxins C3a, C4a, and C5a, Arg-or Lys-enkephalins, epidermal growth factor, and hemoglobin (2, 7, 12, 13). CPM preferentially cleaves C-terminal Arg as exemplified by the kinetics with Arg 6 -Met 5 -enkephalin (K m ϭ 46 M, k cat ϭ 934 min Ϫ1 ) versus Lys 6 -Met 5 -enkephalin (K m ϭ 375 M, k cat ϭ 663 min Ϫ1 ) (2). Bradykinin exhibits the lowest K m (16 M) of any CPM substrate tested (2), a concentration that is still much higher than the typical physiological concentration of this peptide in the nanomolar range. However, peptidases in vivo typically work at substrate concentrations far below the K m as exemplified by angiotensin I-converting enzyme (ACE), which has the same relatively high K m (16 M) with angiotensin I (14), a major physiological substrate. The development of ACE inhibitors as effective agents for treating hypertension and cardiovascular diseases was based in large part on the critical role of this enzyme in converting angiotensin I to II in vivo (15).The kinin peptides bradykinin and kallidin (Lys-bradykinin) are generated by the proteolytic action of plasma or tissue kallikrein on high or low molecular weight kininogen (16,17). Removal of the C-terminal Arg from bradykinin or kallidin inactivates these peptides as agonists of the constitutively expressed B2 receptor (B2R) (16,17). However, this conversion is a required processing step to generate desArg 9 -bradykinin or des-Arg 10 -kallidin (16, 18), metabolites that have a variety of biological activities mediated by specific activation of a different B1 receptor (B1R) whose expression is induced by inflammatory mediators (19,20). Thus, CPM acts as a cell surface processing enzyme to generate des-Arg-kinin agonists for the B1R, and without this catalytic conversion, B1R signaling could not occur. This is of potential importance in inflammatory or pathological responses. For example, B1R activation stimulates extracellular signal-regulated kinase phosphorylation, prostaglandin production (20), and inducible nitric-oxide synthase-mediate...

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“…Both basal and stimulated eNOS activation and relaxations are enhanced in vessels from caveolin-1 (-/-) mice (Drab et al 2001, Razani et al 2001. In addition, the vessels in the microcirculation are hyperpermeable from NO dependent vascular leakage (Razani et al 2002).…”

Section: Regulation Of No Production By Protein-protein Interactions mentioning

confidence: 99%

Regulation of endothelial derived nitric oxide in health and disease

Sessa

2005

Mem. Inst. Oswaldo Cruz

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In the past decade the importance of the vascular endothelium as a multifunctional regulator of vascular smooth muscle physiology and pathophysiology has been appreciated. Indeed, the endothelium responds to hemodynamic stimuli (pressure, shear stress, and wall strain) and locally manufactured mediators (such as bradykinin, prostaglandins, and angiotensin) and in turn can release factors that can influence the adhesion and aggregation of circulating cells to the endothelium and the tone of vascular smooth muscle. In many diseases, including atherosclerosis, diabetes or cirrhosis endothelial dysfunction manifested as an impairment nitric oxide (NO) production or bioactivity may be an early hallmark of disease and a treatable entity. In this chapter, the importance of NO as a mediator of vascular function and potential mechanisms of endothelial NO synthase (eNOS) activation in disease will be discussed. Regulation of vascular tone by endogenous NOeNOS is the NOS isoform responsible for producing the classical endothelium-derived relaxing factor as originally described by (Furchgott & Zawadski 1981). Evidence for the importance of eNOS derived NO in the regulation of vascular tone is based on experiments in animals and in humans demonstrating that L-arginine based inhibitors of NOS increase blood or perfusion pressure and vascular resistance and reduce blood flow in vivo and in vitro. More recently, this has been unequivocally confirmed using mice with targeted disruption of the eNOS gene locus. eNOS knockout mice (-/-) are mildly hypertensive relative to wild-type littermate control mice (+/+) of the same generation. Importantly, the pressor effect of nitro-L-arginine, a NOS inhibi- tor, is attenuated in the -/-mice and endothelium-dependent relaxation in response to acetylcholine is abrogated in isolated vessels (Huang et al. 1995, Shesely et al. 1996. This fundamental finding is direct "proof of-principal" for the major contribution of NO in vasomotor control in large blood vessels. Physiological activation of eNOS and NO releaseTypically, endothelial cells release NO in response to autacoids that mobilize intracellular calcium such as thrombin, VEGF or ADP. The proposed mechanism for eNOS activation is that the released calcium will bind to calmodulin (CaM) and the calcium/CaM complex will bind to the CaM site in the enzyme promote NO synthesis. However, the most physiological agonist for NO release is fluid shear stress. Shear stress in vitro or shear rate in vivo, is the tangential vector of force elicited by the flow of blood over the endothelial cell surface. Exposure of endothelial cells to shear stress results in a burst of NO release, followed by a sustained phase. In vivo, increasing shear rate due to high blood flow will cause flow dependent dilations of certain vascular beds while decreasing shear rate will promote vasoconstriction. Shear induced NO release in vitro and flow-dependent vasodilation in vivo can be blocked with NOS inhibitors. Interestingly, shearinduced NO release appears to "independen...

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Caveolae: From Cell Biology to Animal Physiology

Cited by 888 publications

References 283 publications

Slo1 Caveolin-binding Motif, a Mechanism of Caveolin-1-Slo1 Interaction Regulating Slo1 Surface Expression

Slo1 Caveolin-binding Motif, a Mechanism of Caveolin-1-Slo1 Interaction Regulating Slo1 Surface Expression

Carboxypeptidase M and Kinin B1 Receptors Interact to Facilitate Efficient B1 Signaling from B2 Agonists

Regulation of endothelial derived nitric oxide in health and disease

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