Caveolae as Potential Hijackable Gates in Cell Communication

Abstract

Caveolae are membrane microdomains described in many cell types involved in endocytocis, transcytosis, cell signaling, mechanotransduction, and aging. They are found at the interface with the extracellular environment and are structured by caveolin and cavin proteins. Caveolae and caveolins mediate transduction of chemical messages via signaling pathways, as well as non-chemical messages, such as stretching or shear stress. Various pathogens or signals can hijack these gates, leading to infectious, oncogenic and even caveolin-related diseases named caveolinopathies. By contrast, preclinical and clinical research have fallen behind in their attempts to hijack caveolae and caveolins for therapeutic purposes. Caveolae involvement in human disease is not yet fully explored or understood and, of all their scaffold proteins, only caveolin-1 is being considered in clinical trials as a possible biomarker of disease. This review briefly summarizes current knowledge about caveolae cell signaling and raises the hypothesis whether these microdomains could serve as hijackable "gatekeepers" or "gateways" in cell communication. Furthermore, because cell signaling is one of the most dynamic domains in translating data from basic to clinical research, we pay special attention to translation of caveolae, caveolin, and cavin research into clinical practice.

Lemon‐Derived Extracellular Vesicles Nanodrugs Enable to Efficiently Overcome Cancer Multidrug Resistance by Endocytosis‐Triggered Energy Dissipation and Energy Production Reduction

“…While, both HR and DOX could not down-regulate the expression of CHC and CAV-1 (Figure S26, Supporting Information). CAV-1 is the most important structural protein of caveolae in the surface of many mammalian cells, [36][37][38][39] which plays critical role in caveolin-mediated endocytosis (such as cell signaling, [40][41][42] lipid regulation [43][44][45][46] ) and subsequent cytoplasmic transportation (vesicular transport [47][48][49][50][51] ). It was reported the down-regulation of CAV-1 could promote cholesterol accumulation in mitochondria resulting in mitochondria dysfunction, such as weakening membrane fluidity, reducing ATP, and increasing ROS level.…”

Expression of caveolin family proteins in serum of patients with systemic lupus erythematosus

“…Caveolae represent a subdomain of LR microdomains that are stabilized by caveolin proteins. 37 Caveolins in the content of caveolae are the dominant components of clathrin-independent process called caveolin-dependent endocytosis. 38 In H35 rat hepatoma cells, internalization was identified initiated by antibody binding to myosin 1 at the cell surface.…”

Bilirubin-Induced Neurological Damage: Current and Emerging iPSC-Derived Brain Organoid Models

“…Both HMOX1 and HMOX2 reside in mitochondria, endoplasmic reticulum (ER) and caveolae (membrane micro-domains observed at the interface with the extracellular environment), which might have a correlation with BIND-induced neurocytotoxicity, as various molecular pathways become activated in the course of BIND neurotoxicity. These pathways include inflammation, mitochondrial damage and oxidative stress to ER [ 5 , 54 , 55 ]. The disturbances in mitochondria and ER usually lead to several additional sequelae, such as neuronal excito-toxicity (a complex process triggered by glutamate receptor activation resulting in dendrite degeneration and cell death), mitochondrial energy failure, increased intracellular calcium concentration and deoxyribonucleic acid (DNA) damage ( Figure 1 ) [ 16 , 56 , 57 ].…”