Physical and functional interaction between GalT2 and Calsenilin/Calp

C. QUINTERO; J. VALDEZ-TAUBAS; M. FERRARI; H. MACCIONI

Rosario, Argentina

Congreso; XLII reunión Anual SAIB; 2006

Sociedad Argentina de Investigación en Bioquímica y Biología Celular

Physical and functional interaction between GalT2 and Calsenilin/Calp Cristian Quintero, Javier Valdez Taubas, Mariana Ferrari, Sergio Haedo y Hugo Maccioni. Depto de Química Biológica (CIQUIBIC-CONICET), Fac. De Ciencias Químicas, Univ. Nac. de Córdoba. E-mail: maccioni@dqb.fcq.unc.edu.ar UDP-Gal: GM2 Galactosyltransferase (GalT2) is a Golgi resident, type II membrane protein, involved in the synthesis of glycosphingolipids. The determinants for Golgi localisation are still uncharacterised. In order to identify putative binding partners involved in this process, we carried out a yeast two-hybrid screen using elements of the N-terminal domain of GalT2 (sufficient for Golgi localisation) as bait. We identified Calsenilin, and its close homologue CALP (Calsenilin-like protein), both members of the Neuronal Calcium Sensor (NCS) family of calcium binding proteins. Calp and Calsenilin are involved in the trafficking of potassium channels of the Kv4 family to the plasma membrane, and they also interact with Presenilins, proteins involved in the pathogenesis of Alzheimer disease. The physical interaction between GalT2 and Calsenilin was confirmed by coimmunoprecipitation experiments in cotransfected CHO-K1 cells. In cells, the expression of Calp or Calsenilin shifts a fraction of GalT2-GFP and Mannosidase II (ManII), from the Golgi to the endoplasmic reticulum. This was not observed for the Golgin GM130. In addition, the expression of GalT2 and ManII decreases the half-life of CALP and Calsenilin, in a proteosome dependent fashion. Results suggest that Calp/Calsenilin are involved in the trafficking of subsets of Golgi resident proteins.