Poly ADP-ribosylation: New Localizations and increase in peripheric nerves of Trembler-J Mice

LAURA LAFON-HUGHES; CARLOS ROMEO; KARINA CAL; SALOMÉ VILCHEZ LARREA; SILVIA H. FERNÁNDEZ VILLAMIL; ARCHANA DHASARATHY; SERGEI NECHAEV; GUSTAVO A. FOLLE; JOSÉ R. SOTELO; ALEJANDRA KUN

Cold Spring Harbor

Congreso; PARP family and ADP-ribosylation; 2016

Cold Spring Harbor Laboratories

Poly-ADP-ribosylation (PARylation) is a post-translational protein modification which consists in the addition of succesive ADP-ribose monomers generating variable length poly-ADP-ribose (PAR) chains. PARylation studies have been focused mainly on nuclear proteins. Nevertheless, we have recently reported the presence of PAR associated to the adhesion belt in cultured renal epithelial monkey VERO cells. We have demonstrated that PAR synthesis inhibitors induce cell shape and adhesion changes whereas the actin cytoskeleton disassembly leads to PAR belt disruption, suggesting a structural and functional association between actin and PAR. We investigated whether PARylation is restricted to VERO cell junctions or is also related to the actin cytoskeleton in other tissues. We have explored and detected a PAR belt in intestinal epithelia, epidermis, dermal acini and hepatic capilaries, demonstrating that this phenomenom is extensive to several different epithelial tissues. Considering that we have recently described in peripheral nerve fibers of Trembler-J mice (TrJ mice; murine model of the human peripheric neuropathy Charcot Marie Tooth 1E) significant increases in the expression of the actin cytoskeleton, we have analized PARylation levels in the sciatic nerve of TrJ and wild-type mice. The actin increase correlates with PAR signal increase. Different approaches to validate the anti-PAR antibody in this particular context are discussed. If completely confirmed, our results strongly argue in favor of the structural and functional interaction of actin and PAR whose biological significance remains to be elucidated.