Lack of interaction between acidic nuclear phosphoprotein 32 family member E (ANP32e), protein phosphatase 2A (PP2A) and amino-terminal fragments of mutant huntingtin (Htt) in human neuritic striatal aggregates.

CLAUDIA PERANDONES; COSTANZO RV; FEDERICO EDUARDO MICHELI; RADRIZZANI MARTIN

Buenos Aires

Congreso; 14th International Congress of Parkinson?s Disease and Movement Disorders; 2010

Movement Disorders

Previously we revealed the existence of an association between the Anp32e and PP2A in the synapses of mouse cerebellum using antibodies and oligonucleotide-aptamers. Now we demonstrate the existence of interactions between the proteins Anp32e and huntingtin, assaying co-precipitation, fluorescence-resonance-energy-transfer, confocal microscopy co-localization and the subcellular localization at synapses was seen with electronic microscopies. Aptamers were developed to recognize the amino-terminal of huntingtin protein and was used as affinity column to analyse the proteins associated with the Anp32e/Huntingtin complex. In concordance with the synapses localization, we found interactions between the huntingtin and the Heavy chains of Myosyn-Va Alpha and 10, the Spectrin 2-Alpha and Actin, all related to the fast traffic of vesicles and endocytosis. The distribution of vesicles containing the Anp32e-huntingtin complex was switched by primary synapses contacts in the ataxic mutant mice models "staggerer and weaver" and suggest a role during the synaptogenesis process. ANP32e and PP2A showed interaction with huntingtin in Striatal and Cortical neurons and these proteins were absent in brains of human affected by the Huntington disease (HD). Our results shows that ANP32e, PP2A and huntingtin proteins play a role in fast vesicle transport and suggest that the loss of the interaction between them may be responsible of the selective neuropathology of HD.