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[P189]: Dissection of SLITRK1 signalling in neuronal development
Author(s) -
Grice D.E.,
Buxbaum J.D.,
Sakurai T.,
Vitale R.
Publication year - 2006
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2006.09.249
Subject(s) - mount , grice , editorial board , citation , medical school , medicine , library science , philosophy , computer science , linguistics , medical education , pragmatics , operating system
Multiple cues, including trophic factors and neuronal activity can regulate the growth of mammalian dendrites. In this study we asked whether GSK-3 , a kinase known to be important in axonal growth, also plays a role in dendrite initiation and growth. We show that in cultured sympathetic neurons, GSK-3 is expressed in cell bodies and processes including MAP2-positive dendrites and that GSK-3 activity is repressed in response to cues that promote dendrite formation, such as neurotrophins and neuronal depolarization. Treatment of sympathetic neurons with two potent and selective GSK-3 inhibitors or a dominant-negative mutant of GSK-3 , (dnGSK-3 ) caused a robust increase of the number of primary dendrites as well as of the total dendrite length per cell. Similarly, GSK-3 inhibition promoted dendritic initiation and growth in cortical neurons and in hippocampal neurons in slice cultures, indicating a general requirement for GSK-3 in dendrite formation. We also investigated the targets of GSK-3 activity in the promotion of dendrites. We show that GSK-3 regulates dendrite development in part by inhibiting ERK, a kinase known to regulate dendrite stability and growth. Indeed, inhibition of GSK-3 activity enhanced ERK activity, and suppression of ERK activity blocked dendrite formation. Together these data indicate that GSK-3 is a general negative regulator of dendrite growth. In response to neuronal activity and trophic factors, GSK-3 is phosphorylated and inactivated, likely through a PI3-kinase-integrin-linked kinase (ILK) pathway, and this negative regulation is suppressed, allowing dendrite initiation and growth to proceed.