Katanin p60-like1 promotes microtubule growth and terminal dendrite stability in the larval class IV sensory neurons of Drosophila.
Dendrite shape is considered a defining component of neuronal function. Yet, the mechanisms specifying diverse dendritic morphologies, and the extent to which their function depends on these morphologies, remain unclear. Here, we demonstrate a requirement for the microtubule-severing protein katanin p60-like 1 (Kat-60L1) in regulating the elaborate dendrite morphology and nocifensive functions of Drosophila larval class IV dendritic arborization neurons. Kat-60L1 mutants exhibit diminished responsiveness to noxious mechanical and thermal stimuli. Class IV dendrite branch number and length are also reduced, supporting a correspondence between neuronal function and the full extent of the dendritic arbor. These arborization defects occur particularly in late larval development, and live imaging reveals that Kat-60L1 is required for dynamic, filopodia-like nascent branches to stabilize during this stage. Mutant dendrites exhibit fewer EB1-GFP-labeled microtubules, suggesting that Kat-60L1 increases polymerizing microtubules to establish terminal branch stability and full arbor complexity. Although loss of the related microtubule-severing protein Spastin also reduces the class IV dendrite arbor, microtubule polymerization within dendrites is unaffected. Conversely, Spastin overexpression destroys stable microtubules within these neurons, while Kat-60L1 has no effect. Kat-60L1 thus sculpts the class IV dendritic arbor through microtubule regulatory mechanisms distinct from Spastin. Our data support differential roles of microtubule-severing proteins in regulating neuronal morphology and function, and provide evidence that dendritic arbor development is the product of multiple pathways functioning at distinct developmental stages.
Department of Biology, Duke University, Durham, North Carolina 27708, USA.
Andrea
A
Stewart
Asako
A
Tsubouchi
Melissa M
MM
Rolls
W Daniel
WD
Tracey
Nina Tang
NT
Sherwood
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000166:cytology*; D002454:Cell Differentiation / Q000235:genetics; D003712:Dendrites / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D000074201:Katanin; D007814:Larva / Q000033:anatomy & histology; D008164:Luminescent Proteins / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D009154:Mutation; D059225:Nociception / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000145:classification / Q000166:cytology*
D029721:Drosophila Proteins; C405804:EB1 microtubule binding proteins; D008164:Luminescent Proteins; D008869:Microtubule-Associated Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D000251:Adenosine Triphosphatases; C501874:spas protein, Drosophila; C540495:Kat-60L1 protein, Drosophila; D000074201:Katanin