Reference Report

Reference
Citation	Toda, H., Mochizuki, H., Flores, R., Josowitz, R., Krasieva, T.B., LaMorte, V.J., Suzuki, E., Gindhart, J.G., Furukubo-Tokunaga, K., Tomoda, T. (2008). UNC-51/ATG1 kinase regulates axonal transport by mediating motor-cargo assembly. Genes Dev. 22(23): 3292--3307. (Export to RIS)
FlyBase ID	FBrf0206363
Publication Type	Research paper
PubMed ID	19056884
PubMed Abstract	Axonal transport mediated by microtubule-dependent motors is vital for neuronal function and viability. Selective sets of cargoes, including macromolecules and organelles, are transported long range along axons to specific destinations. Despite intensive studies focusing on the motor machinery, the regulatory mechanisms that control motor-cargo assembly are not well understood. Here we show that UNC-51/ATG1 kinase regulates the interaction between synaptic vesicles and motor complexes during transport in Drosophila. UNC-51 binds UNC-76, a kinesin heavy chain (KHC) adaptor protein. Loss of unc-51 or unc-76 leads to severe axonal transport defects in which synaptic vesicles are segregated from the motor complexes and accumulate along axons. Genetic studies show that unc-51 and unc-76 functionally interact in vivo to regulate axonal transport. UNC-51 phosphorylates UNC-76 on Ser(143), and the phosphorylated UNC-76 binds Synaptotagmin-1, a synaptic vesicle protein, suggesting that motor-cargo interactions are regulated in a phosphorylation-dependent manner. In addition, defective axonal transport in unc-76 mutants is rescued by a phospho-mimetic UNC-76, but not a phospho-defective UNC-76, demonstrating the essential role of UNC-76 Ser(143) phosphorylation in axonal transport. Thus, our data provide insight into axonal transport regulation that depends on the phosphorylation of adaptor proteins.
DOI	10.1101/gad.1734608
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Secondary IDs
Language of Publication	English
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Also Published As
Parent Publication
Publication Type	Journal
Abbreviation	Genes Dev.
Title	Genes & Development
Publication Year	1987-
ISBN/ISSN	0890-9369
Data from Reference
Aberrations (1)
	Df(3L)ED4486
Alleles (13)
	Atg1³ Atg1²⁵ Atg1^EP3348 Atg1^{K38A.Scer\UAS} Atg1^Scer\UAS.cTa Atg1^unspecified Klc^8ex94 Scer\GAL4^elav-C155 Unc-76^ex107 Unc-76^G0360 Unc-76^{S143A.Scer\UAS} Unc-76^{S143D.Scer\UAS} Unc-76^Scer\UAS.cTa
Constructs (5)
	P{UAS-unc-51.K38A} P{UAS-unc-51.WT} P{UAS-Unc-76.S143A} P{UAS-Unc-76.S143D} P{UAS-Unc-76.WT}
Genes (14)
	Aplip1 Atg1 CG42709 Csp Dhc64C futsch Khc Klc Lis-1 Scer\GAL4 syd Syt1 Unc-76 unc-104
Insertions (2)
	P{EP}Atg1^EP3348 P{GawB}elav^C155
Natural transposons (1)
	P-element