Microvascular hyperpermeability in caveolin-1 (-/-) knock-out mice. Treatment with a specific nitric-oxide synthase inhibitor, L-NAME, restores normal microvascular permeability in Cav-1 null mice.

Microvascular permeability is mediated by (i) the caveolar transcytosis of molecules across endothelial cells and (ii) the paracellular movement of ions and nutrients. Recently, we derived Cav-1 (-/-) knock-out mice using standard homologous recombination techniques. These mice are viable but show a loss of endothelial cell caveolae and striking defects in caveolae-mediated endocytosis.

Caveolin-3 knock-out mice develop a progressive cardiomyopathy and show hyperactivation of the p42/44 MAPK cascade.

A growing body of evidence suggests that muscle cell caveolae may function as specialized membrane micro-domains in which the dystrophin-glycoprotein complex and cellular signaling molecules reside. Caveolin-3 (Cav-3) is the only caveolin family member expressed in striated muscle cell types (cardiac and skeletal). Interestingly, skeletal muscle fibers from Cav-3 (-/-) knock-out mice show a number of myopathic changes, consistent with a mild-to-moderate muscular dystrophy phenotype.

Expression of caveolin-1 induces premature cellular senescence in primary cultures of murine fibroblasts.

Caveolae are vesicular invaginations of the plasma membrane. Caveolin-1 is the principal structural component of caveolae in vivo. Several lines of evidence are consistent with the idea that caveolin-1 functions as a "transformation suppressor" protein.

Src-induced phosphorylation of caveolin-2 on tyrosine 19. Phospho-caveolin-2 (Tyr(P)19) is localized near focal adhesions, remains associated with lipid rafts/caveolae, but no longer forms a high molecular mass hetero-oligomer with caveolin-1.

Caveolin-2 is the least well studied member of the caveolin gene family. It is believed that caveolin-2 is an "accessory protein" that functions in conjunction with caveolin-1. At the level of the ER, caveolin-2 interacts with caveolin-1 to form a high molecular mass hetero-oligomeric complex that is targeted to lipid rafts and drives the formation of caveolae.

Familial isolated hyperCKaemia associated with a new mutation in the caveolin-3 (CAV-3) gene.

An 18 year old man and his mother both presented with persistent, isolated raised serum creatine kinase (hyperCKaemia) without muscle symptoms. Analysis of caveolin-3 protein expression in muscle biopsy of the propositus showed a reduction in the protein. Genetic analysis revealed a new heterozygous mutation in the caveolin-3 (CAV-3) gene: a C-->T transition at nucleotide position 83 in exon 1 leading to a substitution of a proline for a leucine at amino acid position 28 (P28L).

Molecular cloning and developmental expression of the caveolin gene family in the amphibian Xenopus laevis.

Caveolae are approximately 50-100 nm invaginations of the plasma membrane thought to form as a result of a local accumulation of cholesterol, sphingolipids, and a unique family of three proteins known as the caveolins: Cav-1, -2, and -3. Here, we report the identification, sequence, and developmental expression of the three caveolin genes in the amphibian Xenopus laevis. Sequence comparisons show that Xenopus Cav-1, -2, and -3 are approximately 80, 64, and 45% identical, respectively, to their counterparts in humans.

Caveolin-1/3 double-knockout mice are viable, but lack both muscle and non-muscle caveolae, and develop a severe cardiomyopathic phenotype.

The caveolin gene family consists of caveolins 1, 2, and 3. Caveolins 1 and 2 are co-expressed in many cell types, such as endothelial cells, fibroblasts, smooth muscle cells and adipocytes, where they form a heteroligomeric complex. In contrast, the expression of caveolin-3 is muscle-specific.

Our results in the treatment of fractures dislocations of Lisfranc's joint.

The authors report their experience in the treatment of traumatic injuries of Lisfranc's joint based on 30 cases treated by surgery between 1984 and 1999. All of the patients were re-evaluated clinically and radiographically. What emerges from the study is the need for surgical stabilization with percutaneous Kirschner wires or by open procedure in cases where there are doubts or where reduction is impossible.

Our experience in the treatment of fractures of the astragalus.

The authors evaluate the results of a series of cases treated by surgery for fractures of the astragalus at the IInd Orthopaedic Division of the University of Pisa between 1978 and 1998. Treatment consisted in reduction and stabilization of the fractures by percutaneous route or by anterolateral approach. Prognosis for fractures of the neck worsens as the Hawkins radiographic classification of degrees increases.

Intracellular retention of glycosylphosphatidyl inositol-linked proteins in caveolin-deficient cells.

The relationship between glycosylphosphatidyl inositol (GPI)-linked proteins and caveolins remains controversial. Here, we derived fibroblasts from Cav-1 null mouse embryos to study the behavior of GPI-linked proteins in the absence of caveolins. These cells lack morphological caveolae, do not express caveolin-1, and show a approximately 95% down-regulation in caveolin-2 expression; these cells also do not express caveolin-3, a muscle-specific caveolin family member.

Connexin family members target to lipid raft domains and interact with caveolin-1.

Lipid rafts are cholesterol-sphingolipid-rich microdomains that function as platforms for membrane trafficking and signal transduction. Caveolae are specialized lipid raft domains that contain the structural proteins known as the caveolins. Connexins are a family of transmembrane proteins that self-associate to form cell-cell connections known as gap junctions and that are linked to cytosolic proteins, forming a protein complex or Nexus.

Mutational analysis identifies a short atypical membrane attachment sequence (KYWFYR) within caveolin-1.

Caveolae are vesicular invaginations of the plasma membrane. Their formation is strictly dependent on the expression of the caveolin coat proteins. During transit to the plasma membrane, approximately 15 monomers of caveolin-1 assemble into a multivalent homo-oligomer.

Caveolin-2-deficient mice show evidence of severe pulmonary dysfunction without disruption of caveolae.

Caveolin-2 is a member of the caveolin gene family with no known function. Although caveolin-2 is coexpressed and heterooligomerizes with caveolin-1 in many cell types (most notably adipocytes and endothelial cells), caveolin-2 has traditionally been considered the dispensable structural partner of the widely studied caveolin-1. We now directly address the functional significance of caveolin-2 by genetically targeting the caveolin-2 locus (Cav-2) in mice.

Rho family GTPases regulate mammary epithelium cell growth and metastasis through distinguishable pathways.

Background: Relatively few genes have been shown to directly affect the metastatic phenotype of breast cancer epithelial cells in vivo. The Rho family of proteins, incluing the Rho, Rac and Cdc42 subfamilies, are related to the small GTP binding protein Ras and regulated diverse biological processes including gene transcription, cytoskeletal organization, cell proliferation and transformation. The effects of Cdc42, Rac and Rho on the actin cytoskeleton suggested a possible role for Rho proteins in cellular motility and metastasis; however, a formal analysis of the role of Rho proteins in breast cancer cellular growth and metastasis in vivo had not previously been performed.

Impairment of caveolae formation and T-system disorganization in human muscular dystrophy with caveolin-3 deficiency.

Caveolin-3, a muscle specific caveolin-related protein, is the principal structural protein of caveolar membranes. We have recently identified an autosomal dominant form of limb girdle muscular dystrophy (LGMD-1C) that is due to caveolin-3 deficiency and caveolin-3 gene mutations. Here, we studied by electron microscopy, including freeze-fracture and lanthanum staining, the distribution of caveolae and the organization of the T-tubule system in caveolin-3 deficient human muscle fibers.

Caveolin-1 expression enhances endothelial capillary tubule formation.

The level of caveolin-1 expression closely correlates with the oncogenic transformation of NIH 3T3 cells, the proliferation of human cancer cells, and the differentiation of adipocytes and muscle cells. However, the role of caveolin-1 in endothelial cell proliferation and differentiation remains unknown. Here, we have shown that angiogenic growth factors that stimulate endothelial cell proliferation lead to dramatic reductions in caveolin-1 expression.

Caveolin-1-deficient mice are lean, resistant to diet-induced obesity, and show hypertriglyceridemia with adipocyte abnormalities.

Caveolae organelles and caveolin-1 protein expression are most abundant in adipocytes and endothelial cells. Our initial report on mice lacking caveolin-1 (Cav-1) demonstrated a loss of caveolae and perturbations in endothelial cell function. More recently, however, observation of the Cav-1-deficient cohorts into old age revealed significantly lower body weights, as compared with wild-type controls.

Ulnar nerve entrapment in Guyon's tunnel by an anomalous palmaris longus muscle with a persisting median artery.

A case of ulnar nerve entrapment in Guyon's tunnel caused by an aberrant palmaris muscle, associated with a patent median artery and duplication of the median nerve, is reported.

Tyrosine phosphorylation of beta-dystroglycan at its WW domain binding motif, PPxY, recruits SH2 domain containing proteins.

beta-Dystroglycan is a ubiquitously expressed integral membrane protein that undergoes tyrosine phosphorylation in an adhesion-dependent manner. However, it remains unknown whether tyrosine-phosphorylated beta-dystroglycan interacts with SH2 domain containing proteins. Here, we show that the tyrosine phosphorylation of beta-dystroglycan is constitutively elevated in v-Src transformed cells.

Caveolae-deficient endothelial cells show defects in the uptake and transport of albumin in vivo.

The role of endothelial cell caveolae in the uptake and transport of macromolecules from the blood-space to the tissue-space remains controversial. To address this issue directly, we employed caveolin-1 gene knock-out mice that lack caveolin-1 protein expression and caveolae organelles. Here, we show that endothelial cell caveolae are required for the efficient uptake and transport of a known caveolar ligand, i.

Prolactin negatively regulates caveolin-1 gene expression in the mammary gland during lactation, via a Ras-dependent mechanism.

Caveolin-1 is a 22-kDa integral membrane protein that has been suggested to function as a negative regulator of mitogen-stimulated proliferation in a variety of cell types, including mammary epithelial cells. Because much of our insight into caveolin-1 function has come from the study of human breast tumor-derived cell lines in culture, the normal physiological regulators of caveolin-1 expression in the mammary gland remain unknown. Here, we examine caveolin-1 expression in mice at different stages of mammary gland development.

Caveolae and caveolin-3 in muscular dystrophy.

Caveolae are vesicular invaginations of the plasma membrane, and function as 'message centers' for regulating signal transduction events. Caveolin-3, a muscle-specific caveolin-related protein, is the principal structural protein of caveolar membrane domains in skeletal muscle and in the heart. Several mutations within the coding sequence of the human caveolin-3 gene (located at 3p25) have been identified.