Tyrosine phosphorylation of tumor cell caveolin-1: impact on cancer progression

et al. 2021

Front. Cell Dev. Biol.

The actin cytoskeleton and membrane-associated caveolae contribute to active processes, such as cell morphogenesis and motility. How these two systems interact and control directional cell migration is an outstanding question but remains understudied. Here we identified a negative feedback between contractile actin assemblies and phosphorylated caveolin-1 (CAV-1) in migrating cells. Cytoplasmic CAV-1 vesicles display actin-associated motilities by sliding along actin filaments or/and coupling to do retrograde flow with actomyosin bundles. Inhibition of contractile stress fibers, but not Arp2/3-dependent branched actin filaments, diminished the phosphorylation of CAV-1 on site Tyr14, and resulted in substantially increased size and decreased motility of cytoplasmic CAV-1 vesicles. Reciprocally, both the CAV-1 phospho-deficient mutation on site Tyr14 and CAV-1 knockout resulted in dramatic AMPK phosphorylation, further causing reduced active level of RhoA-myosin II and increased active level of Rac1-PAK1-Cofilin, consequently led to disordered contractile stress fibers and prominent lamellipodia. As a result, cells displayed depolarized morphology and compromised directional migration. Collectively, we propose a model in which feedback-driven regulation between actin and CAV-1 instructs persistent cell migration.

Section: Contractile Actin Assemblies Are Critical For the Organization And Dynamics Of Cav-1 Vesicles By Disturbing Its Phosphorylation mentioning

confidence: 99%

Feedback-Driven Mechanisms Between Phosphorylated Caveolin-1 and Contractile Actin Assemblies Instruct Persistent Cell Migration

Shi

Wen

et al. 2021

Front. Cell Dev. Biol.

“…Cav-1 drives the formation of flask-shaped membrane invaginations known as caveolae that participate in signaling, clathrin-independent endocytosis, and mechanotransduction ( Tiwari et al, 2016 ). Cav-1 phosphorylation has been associated with cellular processes such as focal adhesion dynamics, cell migration and invasion, cancer cell metabolism, and response to mechanical, oxidative stress ( Wong et al, 2020 ). Adhesion-dependent caveolar endocytosis is genuinely dependent on Cav-1 phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

Dephosphorylation of Caveolin-1 Controls C-X-C Motif Chemokine Ligand 10 Secretion in Mesenchymal Stem Cells to Regulate the Process of Wound Healing

Zhao

et al. 2021

Front. Cell Dev. Biol.

Mesenchymal stem cells (MSCs) secrete cytokines in a paracrine or autocrine manner to regulate immune response and tissue regeneration. Our previous research revealed that MSCs use the complex of Fas/Fas-associated phosphatase-1 (Fap-1)/caveolin-1 (Cav-1) mediated exocytotic process to regulate cytokine and small extracellular vesicles (EVs) secretion, which contributes to accelerated wound healing. However, the detailed underlying mechanism of cytokine secretion controlled by Cav-1 remains to be explored. We show that Gingiva-derived MSCs (GMSCs) could secrete more C-X-C motif chemokine ligand 10 (CXCL10) but showed lower phospho-Cav-1 (p-Cav-1) expression than skin-derived MSCs (SMSCs). Moreover, dephosphorylation of Cav-1 by a Src kinase inhibitor PP2 significantly enhances CXCL10 secretion, while activating phosphorylation of Cav-1 by H2O2 restraints CXCL10 secretion in GMSCs. We also found that Fas and Fap-1 contribute to the dephosphorylation of Cav-1 to elevate CXCL10 secretion. Tumor necrosis factor-α serves as an activator to up-regulate Fas, Fap-1, and down-regulate p-Cav-1 expression to promote CXCL10 release. Furthermore, local applying p-Cav-1 inhibitor PP2 could accelerate wound healing, reduce the expression of α-smooth muscle actin and increase cleaved-caspase 3 expression. These results indicated that dephosphorylation of Cav-1 could inhibit fibrosis during wound healing. The present study establishes a previously unknown role of p-Cav-1 in controlling cytokine release of MSC and may present a potential therapeutic approach for promoting scarless wound healing.

“…Furthermore, the subcellular localization of caveolins has been shown to be located in Golgi apparatus, endoplasmic reticulum (ER), mitochondria, nucleus, peroxisomes, lipid droplets (LDs) (Fridolfsson et al, 2014), and mitochondria-associated membranes (MAMs) (Sala-Vila et al, 2016). The Cav-1 protein sequence consists of four domains: an N-terminal domain (1-81 aa), an oligomerization domain (61-101 aa) including the scaffolding domain (82-101 aa), an intramembrane domain (102-134 aa), and a C-terminal domain (135-178 aa) (Filippini and D'Alessio, 2020;Root et al, 2015;Wong et al, 2020). Both the N-terminus and C-terminus of Cav-1 are exposed to the cytoplasm, and the C-terminal domain contains ubiquitination sites, whereas its N-terminal domain contains two phosphorylation sites: tyrosine-14 (Li et al, 1996b) and serine-80 (Schlegel et al, 2001).…”

Section: Caveolin Familymentioning

confidence: 99%

Caveolin-1 Regulates Cellular Metabolism: A Potential Therapeutic Target in Kidney Disease

et al. 2021

The kidney is an energy-consuming organ, and cellular metabolism plays an indispensable role in kidney-related diseases. Caveolin-1 (Cav-1), a multifunctional membrane protein, is the main component of caveolae on the plasma membrane. Caveolae are represented by tiny invaginations that are abundant on the plasma membrane and that serve as a platform to regulate cellular endocytosis, stress responses, and signal transduction. However, caveolae have received increasing attention as a metabolic platform that mediates the endocytosis of albumin, cholesterol, and glucose, participates in cellular metabolic reprogramming and is involved in the progression of kidney disease. It is worth noting that caveolae mainly depend on Cav-1 to perform the abovementioned cellular functions. Furthermore, the mechanism by which Cav-1 regulates cellular metabolism and participates in the pathophysiology of kidney diseases has not been completely elucidated. In this review, we introduce the structure and function of Cav-1 and its functions in regulating cellular metabolism, autophagy, and oxidative stress, focusing on the relationship between Cav-1 in cellular metabolism and kidney disease; in addition, Cav-1 that serves as a potential therapeutic target for treatment of kidney disease is also described.