PKD2/polycystin-2 induces autophagy by forming a complex with BECN1

Pena-Oyarzun, Daniel; Rodriguez-Pena, Marcelo; Burgos-Bravo, Francesca; Vergara, Angelo; Kretschmar, Catalina; Sotomayor-Flores, Cristian; Ramirez-Sarmiento, Cesar A.; De Smedt, Humbert; Reyes, Montserrat; Perez, William; Torres, Vicente A.; Morselli, Eugenia; Altamirano, Francisco; Wilson, Christian A. M.; Hill, Joseph A; et. al.


Macroautophagy/autophagy is an intracellular process involved in the breakdown of macromolecules and organelles. Recent studies have shown that PKD2/PC2/TRPP2 (polycystin 2, transient receptor potential cation channel), a nonselective cation channel permeable to Ca(2+)that belongs to the family of transient receptor potential channels, is required for autophagy in multiple cell types by a mechanism that remains unclear. Here, we report that PKD2 forms a protein complex with BECN1 (beclin 1), a key protein required for the formation of autophagic vacuoles, by acting as a scaffold that interacts with several co-modulators via its coiled-coil domain (CCD). Our data identified a physical and functional interaction between PKD2 and BECN1, which depends on one out of two CCD domains (CC1), located in the carboxy-terminal tail of PKD2. In addition, depletion of intracellular Ca(2+)with BAPTA-AM not only blunted starvation-induced autophagy but also disrupted the PKD2-BECN1 complex. Consistently, PKD2 overexpression triggered autophagy by increasing its interaction with BECN1, while overexpression of PKD2(D509V), a Ca(2+)channel activity-deficient mutant, did not induce autophagy and manifested diminished interaction with BECN1. Our findings show that the PKD2-BECN1 complex is required for the induction of autophagy, and its formation depends on the presence of the CC1 domain of PKD2 and on intracellular Ca(2+)mobilization by PKD2. These results provide new insights regarding the molecular mechanisms by which PKD2 controls autophagy.

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Título según WOS: PKD2/polycystin-2 induces autophagy by forming a complex with BECN1
Título de la Revista: AUTOPHAGY
Número: 7
Fecha de publicación: 2020


Notas: ISI