Article

CDK5 Serves as a Major Control Point in Neurotransmitter Release

Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA.
Neuron (Impact Factor: 15.05). 09/2010; 67(5):797-809. DOI: 10.1016/j.neuron.2010.08.003
Source: PubMed

ABSTRACT

CDK5 is an important kinase in nervous system function, controlling neural development and postsynaptic signal integration. Here we show that CDK5 plays a major role in controlling neurotransmitter release. Inhibition of CDK5 activity, by either acute or genetic means, leads to profound potentiation of presynaptic function, including unmasking of previously "silent" synapses. Removal of CDK5 activity additionally unlocks access to the resting synaptic vesicle pool, which normally remains recalcitrant to exocytosis and recycling even following prolonged action potential stimuli. Presynaptic CDK5 levels are additionally severely depleted by chronic neuronal silencing, a treatment that is functionally similar to CDK5 knockdown with regard to presynaptic potentiation. Thus CDK5 appears to be an integral element in presynaptic homeostatic scaling, and the resting vesicle pool appears to provide a potent functional presynaptic homeostatic control parameter. These studies thus pinpoint CDK5 as a major control point for modulation of neurotransmitter release in mammalian neurons.

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Available from: Timothy A Ryan, Feb 27, 2014
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    • "Hippocampal CA3–CA1 regions were dissected from 1-to 3-day-old Sprague Dawley rats, dissociated, plated, and transfected as previously described (Kim and Ryan, 2010). All imaging experiments were performed as previously described with laser illumination and EM-CCD image collection (Hoppa et al., 2012) and carried out at 37˚C. "
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    • "Cdk5 has been shown to regulate synaptic vesicle pathways by phosphorylating the dephosphin proteins, such as dynamin I and synaptojanin, that, in turn, are dephosphorylated by the protein phosphatase calcineurin (Matsubara et al., 1996; Cousin et al., 2001; Lee et al., 2004). Interestingly , Kim and Ryan (2010) "
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    • "Therefore, calcineurin activity might be important for the maintenance of spontaneous exocytosis at high levels when membrane cholesterol content is decreased. It is possible that calcineurin activation may increase theMarra et al. 2012), whereas genetic knockdown of calcineurin increased the size of the resting pool (Kim & Ryan, 2010). Another possibility is that calcineurin activity may be required for efficient endocytosis, leading to the formation of 'hot' vesicles with an increased ability to fuse (Rose et al. 2013). "
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