The KIF1A homolog Unc-104 is important for spontaneous release, postsynaptic density maturation and perisynaptic scaffold organization
Name
The KIF1A.pdf
Size
1.48 MB
Format
Adobe PDF
Checksum (MD5)
f3aca30d48b9bcbc47a1541882603eec
Author(s)
Hannan, Shabab B.
Kern, Jeannine V.
Stanchev, Doychin T.
Jahn, Thomas R.
Rasse, Tobias M.
Koc, Baran
Zhang, Yao
Date Issued
March 2017
Journal
Scientific Reports
Publisher
Nature Publishing Group
Citation
Zhang, Yao V. et al. “The KIF1A Homolog Unc-104 Is Important for Spontaneous Release, Postsynaptic Density Maturation and Perisynaptic Scaffold Organization.” Scientific Reports 7 (2017): 38172.
Version
Final published version
Abstract
The kinesin-3 family member KIF1A has been shown to be important for experience dependent neuroplasticity. In Drosophila, amorphic mutations in the KIF1A homolog unc-104 disrupt the formation of mature boutons. Disease associated KIF1A mutations have been associated with motor and sensory dysfunctions as well as non-syndromic intellectual disability in humans. A hypomorphic mutation in the forkhead-associated domain of Unc-104, unc-104[superscript bris], impairs active zone maturation resulting in an increased fraction of post-synaptic glutamate receptor fields that lack the active zone scaffolding protein Bruchpilot. Here, we show that the unc-104[superscript bris]mutation causes defects in synaptic transmission as manifested by reduced amplitude of both evoked and miniature excitatory junctional potentials. Structural defects observed in the postsynaptic compartment of mutant NMJs include reduced glutamate receptor field size, and altered glutamate receptor composition. In addition, we observed marked loss of postsynaptic scaffolding proteins and reduced complexity of the sub-synaptic reticulum, which could be rescued by pre- but not postsynaptic expression of unc-104. Our results highlight the importance of kinesin-3 based axonal transport in synaptic transmission and provide novel insights into the role of Unc-104 in synapse maturation.
MIT Department
Picower Institute for Learning and Memory
Terms of Use
Creative Commons Attribution 4.0 International License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/srep38172
