Molecular Characterization of Caveolin Association with the Golgi Complex: Identification of a Cis-Golgi Targeting Domain in the Caveolin Molecule

Luetterforst, Robert; Stang, Espen; Zorzi, Natasha; Carozzi, Amanda; Way, Michael; Parton, Robert G.

doi:10.1083/jcb.145.7.1443

Cited by 114 publications

(139 citation statements)

References 83 publications

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“…Within the stacks, the highest concentration was noted in cis and medial cisternae. Likewise, caveolin was recently reported to be abundant in cis-Golgi and to have a cis-Golgi targeting domain (Luetterforst et al, 1999). In the ER of contractile smooth muscle cells, CTB-HRP was found all of the way from the nuclear envelope to cisternae just inside the plasma membrane.…”

Section: Caveolae Dynamicsmentioning

confidence: 97%

Differences in Caveolae Dynamics in Vascular Smooth Muscle Cells of Different Phenotypes

Thyberg

2000

Laboratory Investigation

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SUMMARY:Vascular smooth muscle cells shift between two major differentiated states with distinct morphological and functional properties, a contractile and a synthetic phenotype. Here, primary cultures were used to study caveolae expression and dynamics in these cells. The results demonstrate that caveolae are more numerous and more actively interact with intracellular organelles in contractile than in synthetic cells. Immunohistochemistry showed that caveolin-1 was mainly localized to caveolae in contractile cells and partly shifted to Golgi-associated vesicles in synthetic cells, whereas caveolin-2 chiefly appeared in cytoplasmic vesicles in both cases. Cholera toxin B subunit, a ligand of G M1 ganglioside, was internalized via caveolae and carried to endosomes and Golgi-associated vesicles. In contractile cells, it later moved into Golgi and endoplasmic reticulum (ER) cisternae and thus had access to the entire endocytic and exocytic pathways. In contrast, in synthetic cells, the tracer was restricted to the endocytic pathway. Filipin staining similarly disclosed that cholesterol was more widely distributed in contractile than in synthetic cells, with strong labeling of both caveolae and adjacent ER portions. Although no direct continuity between caveolae and ER was detected, it is suggested that cholesterol and other molecules may be translocated between these compartments. The observed differences in caveolae expression and dynamics are likely to be significant for the differences in proliferative capacity and cholesterol transport between contractile and synthetic smooth muscle cells. (Lab Invest 2000, 80:915-929).

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Section: Caveolae Dynamicsmentioning

confidence: 97%

Differences in Caveolae Dynamics in Vascular Smooth Muscle Cells of Different Phenotypes

Thyberg

2000

Laboratory Investigation

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“…The transport depends on critical elements in the molecule required for the proper targeting to intracellular compartments (22,23,53). One of the functions of Cav-1 trafficking appears to the maintenance of cholesterol homeostasis (21).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, caveolins are implicated in polarized vesicular traffic in epithelia (19) and in cholesteroltransport (20,21). The intracellular trafficking apparently depends on a specific amino acid sequence in caveolin (22,23).…”

mentioning

confidence: 99%

Identification of a Novel Domain at the N Terminus of Caveolin-1 That Controls Rear Polarization of the Protein and Caveolae Formation

Sun¹,

Flynn

Castranova

et al. 2007

Journal of Biological Chemistry

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When cells are migrating, caveolin-1, the principal protein component of caveolae, is excluded from the leading edge and polarized at the cell rear. The dynamic feature depends on a specific sequence motif that directs intracellular trafficking of the protein. Deletion mutation analysis revealed a putative polarization domain at the N terminus of caveolin-1, between amino acids 32-60. Alanine substitution identified a minimal sequence of 10 residues ( 46 TKEIDLVNRD 55 ) necessary for caveolin-1 rear polarization. Interestingly, deletion of amino acids 1-60 did not prevent the polarization of caveolin-1 in human umbilical vein endothelial cells or wild-type mouse embryonic fibroblasts because of an interaction of Cav 61-178 mutant with endogenous caveolin-1. Surprisingly, expression of the depolarization mutant in caveolin-1 null cells dramatically impeded caveolae formation. Furthermore, knockdown of caveolae formation by methyl-␤-cyclodextrin failed to prevent wild-type caveolin-1 rear polarization. Importantly, genetic depletion of caveolin-1 led to disoriented migration, which can be rescued by full-length caveolin-1 but not the depolarization mutant, indicating a role of caveolin-1 polarity in chemotaxis. Thus, we have identified a sequence motif that is essential for caveolin-1 rear polarization and caveolae formation.Caveolae are specific microdomains of the plasma membrane that were discovered more than 50 years ago (1). In endothelial cells, numerous vesicles appeared to derive from the uniformly flask-shaped invaginations, suggesting the endocytic potential of caveolae (2). Although the function of caveolae as transport vesicles mediating endocytosis and transcytosis remained obscure (3, 4), the identification, cloning, and characterization of caveolar coat proteins, caveolins, has increased our knowledge of caveolae, and a good body of evidence implicates caveolae in a specialized form of delivery of membrane components, extracellular ligands, bacterial toxins, and nonenveloped virus in several cell types (5-8). The caveolae-mediated endocytic pathway differs from that mediated by clathrincoated pits. It is sensitive to protein kinase C inhibitors and cholesterol depletion (by filipin), and in some cells it is involved in the activation of protein tyrosine kinases (9). Phosphorylation at tyrosine 14 of caveolin-1 (Cav-1) 2 may be required for the internalization of caveolae. The mechanism controlling caveolae trafficking remains unclear, but it apparently involves both microtubule and actin cytoskeletons (10). Surprisingly, using Cav-1 as a marker for caveolae, recent studies demonstrate that caveolae are rich in a variety of signaling molecules, with the implication that caveolae may function in the regulation of signal transduction. Given these views, an attractive hypothesis would be whether caveolae could carry signaling machinery to different locations of the cell to spatially organize signaling events. Indeed, Anderson and colleagues (11) have shown recently that concomitant with the relocation o...

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“…Biochemical Procedures-Protein samples were analyzed by SDSpolyacrylamide gel electrophoresis, and Western blotting was performed as described previously (34).…”

Section: Methodsmentioning

confidence: 99%

Flotillin-1/Reggie-2 Traffics to Surface Raft Domains via a Novel Golgi-independent Pathway

Morrow

Rea

Martin

et al. 2002

Journal of Biological Chemistry

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204

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Flotillins are lipid raft-associated proteins, which have been implicated in neuronal regeneration and insulin signaling. We now show that newly synthesized flotillin-1 reaches the plasma membrane via a Sar1-independent and brefeldin A-resistant targeting pathway. Consistent with post-translational membrane association of flotillin, protease sensitivity experiments suggest that flotillin-1 is not a transmembrane protein but is associated with the cytoplasmic face of the plasma membrane. The N terminus of flotillin contains a prohibitinlike domain (PHB), which shows homology to a number of proteins associated with raft domains including stomatin, podocin, and prohibitin. We show that the PHB domain of flotillin can efficiently target a heterologous protein, green fluorescent protein, to the plasma membrane. Another PHB-containing protein, stomatin, traffics to the plasma membrane via the conventional secretory pathway. Plasma membrane association of both full-length flotillin and the green fluorescent proteintagged PHB domain of flotillin is dependent on palmitoylation and requires a conserved cysteine residue, Cys-34, in the PHB domain. The results identify a novel targeting mechanism for plasma membrane association of flotillin-1 involving a Golgi-independent trafficking pathway, the PHB domain, and palmitoylation.

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Molecular Characterization of Caveolin Association with the Golgi Complex: Identification of a Cis-Golgi Targeting Domain in the Caveolin Molecule

Cited by 114 publications

References 83 publications

Differences in Caveolae Dynamics in Vascular Smooth Muscle Cells of Different Phenotypes

Differences in Caveolae Dynamics in Vascular Smooth Muscle Cells of Different Phenotypes

Identification of a Novel Domain at the N Terminus of Caveolin-1 That Controls Rear Polarization of the Protein and Caveolae Formation

Flotillin-1/Reggie-2 Traffics to Surface Raft Domains via a Novel Golgi-independent Pathway

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