Open AccessTranscriptomics of aged Drosophila motor neurons reveals a matrix metalloproteinase that impairs motor function
Author(s) -
Azpurua Jorge,
Mahoney Rebekah E.,
Eaton Benjamin A.
Publication year - 2018
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12729
Subject(s) - biology , neuromuscular junction , neuroscience , transcriptome , drosophila melanogaster , microbiology and biotechnology , motor neuron , gene expression , genetics , gene , spinal cord
Summary The neuromuscular junction ( NMJ ) is responsible for transforming nervous system signals into motor behavior and locomotion. In the fruit fly Drosophila melanogaster , an age‐dependent decline in motor function occurs, analogous to the decline experienced in mice, humans, and other mammals. The molecular and cellular underpinnings of this decline are still poorly understood. By specifically profiling the transcriptome of Drosophila motor neurons across age using custom microarrays, we found that the expression of the matrix metalloproteinase 1 ( dMMP 1 ) gene reproducibly increased in motor neurons in an age‐dependent manner. Modulation of physiological aging also altered the rate of dMMP 1 expression, validating dMMP 1 expression as a bona fide aging biomarker for motor neurons. Temporally controlled overexpression of dMMP 1 specifically in motor neurons was sufficient to induce deficits in climbing behavior and cause a decrease in neurotransmitter release at neuromuscular synapses. These deficits were reversible if the dMMP 1 expression was shut off again immediately after the onset of motor dysfunction. Additionally, repression of dMMP 1 enzymatic activity via overexpression of a tissue inhibitor of metalloproteinases delayed the onset of age‐dependent motor dysfunction. MMP s are required for proper tissue architecture during development. Our results support the idea that matrix metalloproteinase 1 is acting as a downstream effector of antagonistic pleiotropy in motor neurons and is necessary for proper development, but deleterious when reactivated at an advanced age.