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Roman Serrat"Role of Alex3 in mitochondrial dynamics and Wnt signalling pathways "

Abstract :

The distribution and trafficking of mitochondria in neurons requires a highly coordinated network of molecular mechanisms.
Alex3 protein belongs to the eutherian specific family of genes Armcx, characterized by a high expression on the CNS. The Armcx proteins have a primary bimodal localization, both in nucleus and mitochondria as indicated by their putative domains. Overexpression of Armcx proteins causes a profound alteration on the mitochondrial net showing that this family of proteins plays an important role in the regulation of the mitochondrial dynamics. At least, the overexpression of Alex3 protein neither changes the bioenergetic parameters of mitochondria nor alters the mitochondrial fusion/fission rate. Both the overexpression and knock-down of Alex3 and Armc10 proteins in hippocampal neurons alters the mitochondrial distribution and transport. Alex3 and Armc10 interact with the Kinesin/Miro/Trak2 mitochondrial transport regulator complex, suggesting that the Armcx protein family regulates mitochondrial trafficking through this complex. On the other hand, the Wnt signalling pathway induces the degradation of Alex3 protein. This degradation is independent of several Wnt canonical and non-canonical members but we show that PKC and CKII members play a principal role in the control and degradation of Alex3 protein levels. Moreover, Alex3-Wnt dependent degradation reverts the mitochondrial aggregation phenotypes and is avoided by PKC activation, suggesting that Wnt proteins can play a role in the control of mitochondrial dynamics through the regulation of Armcx proteins. Our data point to relevant functions of the Armcx gene cluster in the function of the nervous system and a novel link between mitochondrial dynamics.

Selected publications

The Eutherian Armcx genes regulate mitochondrial trafficking in neurons and interact with Miro and Trak2.
López-Doménech G, Serrat R, Mirra S, D'Aniello S, Somorjai I, Abad A, Vitureira N, García-Arumí E, Alonso MT, Rodriguez-Prados M, Burgaya F, Andreu AL, García-Sancho J, Trullas R, Garcia-Fernàndez J, Soriano E.
Nat Commun. 2012 May 8;3:814. doi: 10.1038/ncomms1829.

Giovanni Marsicano du Neurocentre