Neuronal Lamin regulates motor circuit integrity and controls motor function and lifespan

Authors:

Lisa J. Oyston1,2,3, Yong Qi Lin1, Thang M. Khuong1, Qiao-Ping Wang1, Man Tat Lau1, Teleri Clark1 and G. Gregory Neely1
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Affiliations:

1 The Dr. John and Anne Chong Lab for Functional Genomics, Charles Perkins Centre and School of Life and Environmental Sciences, The University of Sydney NSW 2006, Australia.

2 Neuroscience Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia.

3 St Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney NSW 2052, Australia.

Keywords: 

aging, Lamin, dopaminergic neurons, neurodegeneration, Drosophila, synapse.

Abbreviations:

DA –dopaminergic,

DLM – dorsal longitudinal muscle,

GFS – giant fiber system,

PAM – protocerebral anterior medial,

TTM – tergotrochanteral muscle.

Corresponding Author(s):

G. Gregory Neely, T: +61 2 8627 0519 greg.neely@sydney.edu.au Lisa Oyston, T: +61 2 8627 5061 lisa.oyston@sydney.edu.au

Conflict of interest statement:

None declared.

Please cite this article as:

Lisa J. Oyston, Yong Qi Lin, Thang M. Khuong, Qiao-Ping Wang, Man Tat Lau, Teleri Clark and G. Gregory Neely (2018). Neuronal Lamin regulates motor circuit integrity and controls motor function and lifespan. Cell Stress 2(9): 225-232. doi: 10.15698/cst2018.09.152

© 2018 Oyston et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.

Abstract:

Neuronal aging involves a progressive decline in cognitive abilities and loss of motor function. Mutations in human Lamin genes (LMNA, LMNB1, LMNB2) lead to a wide-range of diseases including muscular dystrophy, peripheral neuropathy and progeria. Here we investigate the role of neuronal Lamin in regulating age-related phenotypes. Neuronal targeting of Lamin led to shortened lifespan, progressive impairment of motor function and loss of dopaminergic (DA) neurons within the protocerebral anterior medial (PAM) cluster in the Drosophila melanogaster brain. Loss of neuronal Lamin caused an age-related decline in neural physiology, with slower neurotransmission and increased chance of motor circuit failure with age. Unexpectedly, Lamin-dependent decline in motor function was specific for the chemical synapses of the dorsal longitudinal muscle (DLM). Together these findings highlight a central role for Lamin dysfunction in regulating neuronal survival and motor circuit physiology during aging.