Src in synaptic transmission and plasticity.
In the central nervous system (CNS), Src and other Src family kinases are widely expressed and are abundant in neurons. Src has been implicated in proliferation and differentiation during the development of the CNS. But Src is highly expressed in fully differentiated neurons in the developed CNS, implying additional functions of this kinase. Over the past decade, a large body of evidence has accumulated showing that a main function of Src is to upregulate the activity of N-methyl-D-aspartate (NMDA) receptors and other ion channels. NMDA receptors (NMDARs) are a principal subtype of glutamate receptors, which mediate fast excitatory transmission at most central synapses. In this review, we focus on Src as a regulator of NMDARs and on the role of Src in NMDAR-dependent synaptic plasticity. We also describe recent studies that give insights into the regulation of Src itself at glutamatergic synapses. By upregulating the function of NMDARs, Src gates the production of NMDAR-dependent synaptic potentiation and plasticity. Thus, Src may be critical for processes underlying physiological plasticity, including learning and memory, and pathological plasticity, such as pain and epilepsy.
Programme in Brain and Behaviour, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada M5G 1X8.
Lorraine V
LV
Kalia
Jeffrey R
JR
Gingrich
Michael W
MW
Salter
D000818:Animals; D002490:Central Nervous System / Q000502:physiology; D006801:Humans; D017434:Protein Structure, Tertiary; D017027:Protein Tyrosine Phosphatases / Q000502:physiology; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D019061:src-Family Kinases / Q000502:physiology*
D016194:Receptors, N-Methyl-D-Aspartate; D019061:src-Family Kinases; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C082101:Ptpn5 protein, mouse