INIMEC - CONICET   05467
INSTITUTO DE INVESTIGACION MEDICA MERCEDES Y MARTIN FERREYRA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Regulation of spine density and morphology by IQGAP1 protein domains.
Autor/es:
IGNACIO JAUSORO, IVAN MESTRES, MONICA REMEDI, MONICA SANCHEZ AND ALFREDO CACERES
Lugar:
Buenos Aires
Reunión:
Simposio; 5th Special Conference of the International Society for Neurochemistry (ISN) “Synapses and dendritic spines in health and disease”.; 2012
Institución organizadora:
International Society of Neurochemistry
Resumen:
IQGAP1 is a scaffolding protein with multiple binding partners, widely expressed among different cell types, including neurons, capable of linking Rho-GTPase signaling with cytosleletal elements and environmental cues. Mice lacking IQGAP1 exhibit marked long-term memory defects, reduce spine number, lower levels of surface NR2A and impaired ERK activity compared with their wild type counterparts. IQGAP1 and the microtubule plus-end tracking protein, CLIP-170 cooperatively regulate dendritic arbor growth in both cortical and hippocampal pyramidal neurons. Based on these observations and to gain further insights into the neuronal functions of IQGAP1, in the present study we used several deletion mutants to explore domains of IQGAP1 that could be necessary for spine and synapse formation. Spine number and shape were assessed by IQGAP1 immunofluorescence or GFP (RFP) fluorescence and the presence of synapses by co-expressing PSD-95 and/or co-staining with synpatophysin. The results obtained suggest a differential role for IQGAP1 domains in spine morphogenesis, in which a region of the N-terminal domain, containing actin and N-WASP binding sites, is required for spine head formation and a region containing the Cdc42 and Rac binding motifs for spine stalk/neck extension. IQGAP1-mediated spine head formation requires N-WASP-Arp 2/3 expression, while stalk extension Cdc42 activity. No alterations in spine number or morphology were observed after expression of IQGAP1 mutants lacking the C-terminal domain.