TMEM184b promotes axon degeneration and neuromuscular junction maintenance

Martha R.C. Bhattacharya, Stefanie Geisler, Sara K. Pittman, Ryan A. Doan, Conrad C. Weihl, Jeffrey Milbrandt, Aaron DiAntonio

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Complex nervous systems achieve proper connectivity during development and must maintain these connections throughout life. The processes of axon and synaptic maintenance and axon degeneration after injury are jointly controlled by a number of proteins within neurons, including ubiquitin ligases and mitogen activated protein kinases. However, our understanding of these molecular cascades is incomplete. Here we describe the phenotype resulting from mutation of TMEM184b, a protein identified in a screen for axon degeneration mediators. TMEM184b is highly expressed in the mouse nervous system and is found in recycling endosomes in neuronal cell bodies and axons. Disruption of TMEM184b expression results in prolonged maintenance of peripheral axons following nerve injury, demonstrating a role for TMEM184b in axon degeneration. In contrast to this protective phenotype in axons, uninjured mutant mice have anatomical and functional impairments in the peripheral nervous system. Loss of TMEM184b causes swellings at neuromuscular junctions that become more numerous with age, demonstrating that TMEM184b is critical for the maintenance of synaptic architecture. These swellings contain abnormal multivesicular structures similar to those seen in patients with neurodegenerative disorders. Mutant animals also show abnormal sensory terminal morphology. TMEM184b mutant animals are deficient on the inverted screen test, illustrating a role for TMEM184b in sensory-motor function. Overall, we have identified an important function for TMEM184b in peripheral nerve terminal structure, function, and the axon degeneration pathway.

Original languageEnglish
Pages (from-to)4681-4689
Number of pages9
JournalJournal of Neuroscience
Volume36
Issue number17
DOIs
StatePublished - Apr 27 2016

Keywords

  • Autophagy
  • Axon degeneration
  • Intraepidermal nerve fibers
  • Mouse
  • Neuromuscular junction

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