Projects per year
Abstract
Microtubules are fundamental elements of neuronal structure and function. They are dynamic structures formed from protofilament chains of α- and β-tubulin heterodimers. Acetylation of the lysine 40 (K40) residue of α-tubulin protects microtubules from mechanical stresses by imparting structural elasticity. The enzyme responsible for this acetylation event is MEC-17/αTAT1. Despite its functional importance, however, the consequences of altered MEC-17/αTAT1 levels on neuronal structure and function are incompletely defined. Here we demonstrate that overexpression or loss of MEC-17, or of its functional paralogue ATAT-2, causes a delay in synaptic branch extension, and defective synaptogenesis in the mechanosensory neurons of Caenorhabditis elegans. Strikingly, by adulthood, the synaptic branches in these animals are lost, while the main axon shaft remains mostly intact. We show that MEC-17 and ATAT-2 regulate the stability of the synaptic branches largely independently from their acetyltransferase domains. Genetic analyses reveals novel interactions between both mec-17 and atat-2 with the focal adhesion gene zyx-1/Zyxin, which has previously been implicated in actin remodelling. Together, our results reveal new, acetylation-independent roles for MEC-17 and ATAT-2 in the development and maintenance of neuronal architecture.
Original language | English |
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Article number | 14003 |
Number of pages | 14 |
Journal | Scientific Reports |
Volume | 12 |
Issue number | 1 |
DOIs | |
Publication status | Published - 17 Aug 2022 |
Projects
- 5 Finished
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Decoding mechanisms of brain-intestinal communication
Pocock, R. (Primary Chief Investigator (PCI))
National Health and Medical Research Council (NHMRC) (Australia)
1/01/18 → 31/12/22
Project: Research
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Decoding Conserved Mechanisms That Control Neuronal Migration
Pocock, R. (Primary Chief Investigator (PCI))
National Health and Medical Research Council (NHMRC) (Australia)
1/01/16 → 31/12/18
Project: Research
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Uncovering the molecular mechanisms behind Charcot-Marie-Tooth disease
Neumann, B.
National Health and Medical Research Council (NHMRC) (Australia)
1/01/16 → 31/12/18
Project: Research
Equipment
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Monash Micro Imaging
Firth, S. (Manager), Fulcher, A. (Operator), Chernyavskiy, O. (Operator), Rzeszutek, M. (Other), Potter, D. (Manager), Hilsenstein, V. (Operator), Nunez-Iglesias, J. (Other), Cody, S. (Manager), Carmichael, I. (Operator), Kouskousis, B. (Other), Creed, S. (Manager) & Ballerin, G. (Operator)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility