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.
Highlights
The term “caveolae” is more than 60 years old and traces back to seminal electron microscopy studies conducted independently by G.E
Further research revealed that caveolae and their scaffold proteins are involved in specific cellular processes, such as plasma microdomain organization and cell signaling (Boscher and Nabi, 2012)—in both normal cells (Sowa, 2012) or tumor cells (Hehlgans and Cordes, 2011)— or even in a specific kind of tumor (Parat and Riggins, 2012)
This review briefly summarizes the knowledge in caveolae cell signaling and assesses the status of these microdomains as both gatekeepers and gateways in cell communication
Summary
The term “caveolae” is more than 60 years old and traces back to seminal electron microscopy studies conducted independently by G.E. The role for caveolins as guardians against oncogenic transformation is supported by reports that loss of Cav-1 in tumor-associated fibroblasts drives a change in phenotype from “normal” to “fuel-supplier,” modifying the stromal environment of cancer cells into a medium favoring survival (Mercier et al, 2008; Trimmer et al, 2011) This suppressor status has been challenged over time, with some limited but fairly consistent evidence of Cav-1 overexpression in various types of cancer. Prions PrP(C) were shown to be associated in rafts with caveolin-1 and signaling molecules, including Fyn and Src tyrosine kinases (Taylor and Hooper, 2006; Toni et al, 2006) These data open the avenue for exploring conditions in which cell are handling prionlike proteins (i.e., neurodegenerative diseases; Muradashvili et al, 2016; Puangmalai et al, 2020). Molecular modeling and simulation have suggested the existence of caveolin-binding sites for SARS-CoV proteins “SARS coronavirus entry into host cells through a clathrin- and caveolae-independent endocytic pathway”
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