Neuronal Lamin regulates motor circuit integrity and controls motor function and lifespan
Lisa J. Oyston,
Yong Qi Lin,
Thang M. Khuong,
Qiao-Ping Wang,
Man Tat Lau,
Teleri Clark,
G. Gregory Neely
Affiliations
Lisa J. Oyston
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.
Yong Qi Lin
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.
Thang M. Khuong
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.
Qiao-Ping Wang
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.
Man Tat Lau
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.
Teleri Clark
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.
G. Gregory Neely
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.
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.
