The Presence of Active Cdk5 Associated with p35 in Astrocytes and Its Important Role in Process Elongation of Scratched Astrocyte

Cdk5/p35; astrocyte; injury; hypertrophy; scratch Cyclin-dependent kinase 5 (Cdk5) is a unique member of the Cdk family; its kinase activity requires association with its activator, p35 or p39. p35 is the strongest and best char-acterized activator. Previous studies showed that p35 is a neuron-specific protein that restricts Cdk5 activity in neu-rons. However, a high expression level of Cdk5 is found in astrocytes, which raises the possibility that astrocytic Cdk5 is functional. Here we show the presence of functional Cdk5 associated with p35 in astrocytes and demonstrate its important role in process elongation of scratched astrocytes. We found that p35 and glial fibrillary acidic protein (GFAP) were co-localized in primary cultured and acute isolated brain cells. Cdk5 could form an immunocomplex with p35 and its activity was shown in pure primary cultured astro-cytes. p35 was upregulated in astrocytes injured by scratch-ing, concomitantly with upregulation of Cdk5 kinase activ-ity. Pretreatment of the scratched astrocytes with a Cdk5 inhibitor, roscovitine, could delay wound healing by inhibi-ting the reorganization of tubulin, GFAP, and the extension of hypertrophic processes. Moreover, overexpression of dom-inant negative Cdk5 could shorten the length of extending protrusion of reactive astrocytes. Thus, our findings demon-strated that functional Cdk5, associated with p35, was expressed in astrocytes and its activity could be upregu-lated in reactive astrocytes, a new role of Cdk5 that has never been reported in the nervous system. The present study may provide new insight for understanding the mul-tifunctional protein complex Cdk5/p35 in the nervous system. VC 2007 Wiley-Liss, Inc