TY - JOUR
T1 - Dynamin 3 is a component of the postsynapse, where it interacts with mGluR5 and Homer
AU - Gray, Noah W.
AU - Fourgeaud, Lawrence
AU - Huang, Bing
AU - Chen, Jing
AU - Cao, Hong
AU - Oswald, Barbara J.
AU - Hémar, Agnès
AU - McNiven, Mark A.
N1 - Funding Information:
We would like to thank Xiaoyun Wang and Mu-Ming Poo for assistance with the hippocampal neuronal cultures; Vanda Lennon, Doug Murphy, Teiichi Furuichi, and Peter McPherson for the kind gifts of antibodies; Enrique Torre for advice concerning immunocytochemistry; Dave Zacharias for neuronal transfection protocols; and Heather Thompson for critically reading this manuscript. N.W.G. is supported by National Institutes of Health Neuroscience Training Grant NS07424.
PY - 2003/3/18
Y1 - 2003/3/18
N2 - The dynamins comprise a large family of mechanoenzymes known to participate in membrane modeling events [1, 2]. All three conventional dynamin genes (Dyn1, Dyn2, Dyn3) are expressed in mammalian brain and produce more than 27 different dynamin proteins as a result of alternative splicing [3]. Past studies have suggested that Dyn1 participates in specialized neuronal functions such as rapid synaptic vesicle recycling [4], while Dyn2 may mediate the conventional clathrin-mediated uptake of surface receptors [5]. Currently, the distribution, expression, and function of Dyn3 in neurons, or in any other cell type, are completely undefined. Here, we demonstrate that Dyn1 and Dyn3 localize differentially in the synapse. Dyn1 concentrates within the presynaptic compartment, while Dyn3 localizes to dendritic spine tips. Within the postsynaptic density (PSD), we found Dyn3, but not Dyn1, to be part of a biochemically isolated complex comprised of Homer and metabotropic glutamate receptors. Finally, although dominant-negative Dyn3 did not seem to inhibit receptor endocytosis, overexpression of a specific Dyn3 spliced variant in mature neurons caused a marked remodeling of dendritic spines. These data suggest that Dyn3 is a postsynaptic dynamin and, like its binding partner Homer, plays a significant role in dendritic spine morphogenesis and remodeling.
AB - The dynamins comprise a large family of mechanoenzymes known to participate in membrane modeling events [1, 2]. All three conventional dynamin genes (Dyn1, Dyn2, Dyn3) are expressed in mammalian brain and produce more than 27 different dynamin proteins as a result of alternative splicing [3]. Past studies have suggested that Dyn1 participates in specialized neuronal functions such as rapid synaptic vesicle recycling [4], while Dyn2 may mediate the conventional clathrin-mediated uptake of surface receptors [5]. Currently, the distribution, expression, and function of Dyn3 in neurons, or in any other cell type, are completely undefined. Here, we demonstrate that Dyn1 and Dyn3 localize differentially in the synapse. Dyn1 concentrates within the presynaptic compartment, while Dyn3 localizes to dendritic spine tips. Within the postsynaptic density (PSD), we found Dyn3, but not Dyn1, to be part of a biochemically isolated complex comprised of Homer and metabotropic glutamate receptors. Finally, although dominant-negative Dyn3 did not seem to inhibit receptor endocytosis, overexpression of a specific Dyn3 spliced variant in mature neurons caused a marked remodeling of dendritic spines. These data suggest that Dyn3 is a postsynaptic dynamin and, like its binding partner Homer, plays a significant role in dendritic spine morphogenesis and remodeling.
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U2 - 10.1016/S0960-9822(03)00136-2
DO - 10.1016/S0960-9822(03)00136-2
M3 - Article
C2 - 12646135
AN - SCOPUS:0037452948
SN - 0960-9822
VL - 13
SP - 510
EP - 515
JO - Current Biology
JF - Current Biology
IS - 6
ER -