The kinesin-3, unc-104 regulates dendrite morphogenesis and synaptic development in Drosophila.
The kinesin-3, unc-104 regulates dendrite morphogenesis and synaptic development in Drosophila.
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DOI：
10.1534/genetics.113.151639
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发表时间：
2013-09
期刊：
影响因子：
3.3
通讯作者：
Rasse TM
中科院分区：
文献类型：
--
作者：
Kern JV;Zhang YV;Kramer S;Brenman JE;Rasse TM
Kinesin-based transport is important for synaptogenesis, neuroplasticity, and maintaining synaptic function. In an anatomical screen of neurodevelopmental mutants, we identified the exchange of a conserved residue (R561H) in the forkhead-associated domain of the kinesin-3 family member Unc-104/KIF1A as the genetic cause for defects in synaptic terminal- and dendrite morphogenesis. Previous structure-based analysis suggested that the corresponding residue in KIF1A might be involved in stabilizing the activated state of kinesin-3 dimers. Herein we provide the first in vivo evidence for the functional importance of R561. The R561H allele (unc-104bris) is not embryonic lethal, which allowed us to investigate consequences of disturbed Unc-104 function on postembryonic synapse development and larval behavior. We demonstrate that Unc-104 regulates the reliable apposition of active zones and postsynaptic densities, possibly by controlling site-specific delivery of its cargo. Next, we identified a role for Unc-104 in restraining neuromuscular junction growth and coordinating dendrite branch morphogenesis, suggesting that Unc-104 is also involved in dendritic transport. Mutations in KIF1A/unc-104 have been associated with hereditary spastic paraplegia and hereditary sensory and autonomic neuropathy type 2. However, we did not observe synapse retraction or dystonic posterior paralysis. Overall, our study demonstrates the specificity of defects caused by selective impairments of distinct molecular motors and highlights the critical importance of Unc-104 for the maturation of neuronal structures during embryonic development, larval synaptic terminal outgrowth, and dendrite morphogenesis.
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影响因子：
4.5
作者：
Füger P;Sreekumar V;Schüle R;Kern JV;Stanchev DT;Schneider CD;Karle KN;Daub KJ;Siegert VK;Flötenmeyer M;Schwarz H;Schöls L;Rasse TM
通讯作者：
Rasse TM
影响因子：
25
作者：
Hoogenraad, CC;Milstein, AD;Sheng, M
通讯作者：
Sheng, M
影响因子：
5.3
作者：
Marrus, SB;Portman, SL;DiAntonio, A
通讯作者：
DiAntonio, A
影响因子：
3.3
作者：
Barkus, Rosemarie V.;Klyachko, Olga;Saxton, William M.
通讯作者：
Saxton, William M.
影响因子：
5.5
作者：
BLISS, TVP;LOMO, T
通讯作者：
LOMO, T