Axons connect neurons across great distances in the nervous system, and this distance is a fundamental vulnerability for neurons. Maintenance of functional connectivity requires robust mechanisms for transporting proteins and organelles, in addition to mechanisms for local synthesis of proteins distant from the cell body. Glial cells also provide important local support to axons and synapses. Axons are therefore vulnerable to stressors that impair energy metabolism, cytoskeleton, axonal transport machinery and glial support as well as acute physical injury.
The Collins lab is particularly interested in cellular mechanisms of plasticity that allow the nervous system to adapt to impairments in axons. These include cell autonomous signaling pathways that become triggered in damaged axons, and neuron-glial interactions that mediate circuit adaptations to axonal damage.
Our lab uses both Drosophila melanogaster and mice as model organisms, when enables us to combine molecular genetics approaches with cell biology, biochemistry and primary cell culture to study conserved pathways of axonal damage response.
Insolera R, Lőrincz P, Wishnie, AJ, Juhász, Collins CA. Mitochondrial fission, integrity and clearance require separable functions of Vps13D in Drosophila neurons. Plos Genetics, 2021 Aug 12;17(8):e1009731. PMID: 34383748.
Hao Y, Waller TJ, Nye DM, Li J, Yang Y, Hume RI, Rolls MM, Collins CA. Degeneration of Injured axons and dendrites requires restraint of a protective JNK signaling pathway by the transmembrane protein Raw. J Neurosci. 2019 Oct Oct 23;39(43):8457-8470. PMID: 31492772.
Asgari Adib E, Smithson LJ, Collins CA. An axonal stress response pathway: degenerative and regenerative signaling by DLK. Curr Opin Neurobiol. 2018 Dec; 53: 110-119. PMID: 30053694.
Li J, Zhang YV, Asghari Adib E, Stanchev DT, Xiong X, Klinedinst S, Soppina P, Jahn TR, Hume RI, Rasse TM, Collins CA. Restraint of presynaptic protein levels by Wnd/DLK signaling mediates synaptic defects associated with the kinesin-3 motor Unc-104. Elife. 2017 Sep 19;6 PMID: 28925357.
Hao Y, Frey E, Yoon C, Wong H, Nestorovski D, Holzman LB, Giger RJ, DiAntonio A, Collins CA. An evolutionarily conserved mechanism for cAMP elicited axonal regeneration involves direct activation of the dual leucine zipper kinase DLK. Elife. 2016 Jun 7;5PubMed PMID: 27268300.
Xiong X, Hao Y, Sun K, Li J, Li X, Mishra B, Soppina P, Wu C, Hume RI, Collins CA. The Highwire ubiquitin ligase promotes axonal degeneration by tuning levels of Nmnat protein. PLoS Biol. 2012;10(12):e1001440. PMID: 23226106.
Xiong X, Wang X, Ewanek R, Bhat P, Diantonio A, Collins CA. Protein turnover of the Wallenda/DLK kinase regulates a retrograde response to axonal injury. J Cell Biol. 2010 Oct 4;191(1):211-23. PMID: 20921142.
Collins CA, Wairkar YP, Johnson SL, DiAntonio A. Highwire restrains synaptic growth by attenuating a MAP kinase signal. Neuron. 2006 Jul 6;51(1):57-69. PubMed PMID: 16815332.