Intact caveolae are required for proper extravillous trophoblast migration and differentiation

REPPETTI, JULIETA; RECA, ALEJANDRA; SEYAHIAN, E. ABRIL ; MEDINA, YOLLYSETH; MARTÍNEZ, NORA; SZPILBARG, NATALIA; DAMIANO, ALICIA E.

JOURNAL OF CELLULAR PHYSIOLOGY

WILEY-LISS, DIV JOHN WILEY & SONS INC

Año: 2019 vol. 235 p. 3382 - 3392

0021-9541

Caveolae constitute membrane domains critical for the organization and synchronization of different signaling molecules related to numerous cell processes such as cell migration, invasion, and differentiation. Caveolin‐1 (Cav‐1) is the main integral membrane protein of these domains. Recently, it was found that a normal expression of aquaporin‐3 (AQP3) is required for extravillous trophoblast (EVT) cell migration.Our aim was to investigate the role of caveolae in the migration, invasion, andendovascular differentiation of human EVT cells during placentation and itsinteraction with AQP3. EVT cells (Swan 71 cell line) were cultured in completeDulbecco?s modified Eagle?s medium?nutrient mixture F12 and treated with 5mMmethyl‐β‐cyclodextrin (MβCD) to disrupt caveolae. We found that after MβCDtreatment, Cav‐1 protein was undetectable. In this condition, the ability of the cells to migrate was significantly decreased compared with the control cells, while no differences were observed in the number of invading cells and the metalloproteinases activity between control and MβCD‐treated cells. Surprisingly, the disruption of caveolae significantly enhanced EVT endovascular differentiation. On the contrary, the silencing of AQP3, negatively affected tube‐like formation. The theoretical analysis of the primary sequence of AQP3 protein revealed a putative Cav‐1‐binding site. In addition, immunoprecipitation and double immunofluorescence assays showed that AQP3 colocalized with Cav‐1. These results showed that during placentation an intact caveola in EVT cells may be necessary for AQP3 and Cav‐1 interaction and any perturbations might result in serious pregnancy disorders.