The Drosophila KIF1A Homolog unc-104 Is Important for Site-Specific Synapse Maturation
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Hannan, Shabab B.; Stapper, Zeenna A.; Kern, Jeannine V.; Jahn, Thomas R.; Rasse, Tobias M.; Zhang, Yao; ... Show more Show less
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Mutations in the kinesin-3 family member KIF1A have been associated with hereditary spastic paraplegia (HSP), hereditary and sensory autonomic neuropathy type 2 (HSAN2) and non-syndromic intellectual disability (ID). Both autosomal recessive and autosomal dominant forms of inheritance have been reported. Loss of KIF1A or its homolog unc-104 causes early postnatal or embryonic lethality in mice and Drosophila, respectively. In this study, we use a previously described hypomorphic allele of unc-104, unc-104[superscript bris], to investigate the impact of partial loss-of-function of kinesin-3 on synapse maturation at the Drosophila neuromuscular junction (NMJ). Unc-104[superscript bris] mutants exhibit structural defects where a subset of synapses at the NMJ lack all investigated active zone (AZ) proteins, suggesting a complete failure in the formation of the cytomatrix at the active zone (CAZ) at these sites. Modulating synaptic Bruchpilot (Brp) levels by ectopic overexpression or RNAi-mediated knockdown suggests that the loss of AZ components such as Ca[superscript 2+] channels and Liprin-α is caused by impaired kinesin-3 based transport rather than due to the absence of the key AZ organizer protein, Brp. In addition to defects in CAZ assembly, unc-104[superscript bris] mutants display further defects such as depletion of dense core and synaptic vesicle (SV) markers from the NMJ. Notably, the level of Rab3, which is important for the allocation of AZ proteins to individual release sites, was severely reduced at unc-104[superscript bris] mutant NMJs. Overexpression of Rab3 partially ameliorates synaptic phenotypes of unc-104[superscript bris] larvae, suggesting that lack of presynaptic Rab3 contributes to defects in synapse maturation.
Date issued
2016-09Department
Massachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences; Picower Institute for Learning and MemoryJournal
Frontiers in Cellular Neuroscience
Publisher
Frontiers Research Foundation
Citation
Zhang, Yao V. et al. “The Drosophila KIF1A Homolog Unc-104 Is Important for Site-Specific Synapse Maturation.” Frontiers in Cellular Neuroscience 10 (2016): n. pag.
Version: Final published version
ISSN
1662-5102