Complement protein C1q modulates neurite outgrowth in vitro and spinal cord axon regeneration in vivo

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Sheri L PetersonAileen J Anderson

Abstract

Traumatic injury to CNS fiber tracts is accompanied by failure of severed axons to regenerate and results in lifelong functional deficits. The inflammatory response to CNS trauma is mediated by a diverse set of cells and proteins with varied, overlapping, and opposing effects on histological and behavioral recovery. Importantly, the contribution of individual inflammatory complement proteins to spinal cord injury (SCI) pathology is not well understood. Although the presence of complement components increases after SCI in association with axons and myelin, it is unknown whether complement proteins affect axon growth or regeneration. We report a novel role for complement C1q in neurite outgrowth in vitro and axon regrowth after SCI. In culture, C1q increased neurite length on myelin. Protein and molecular assays revealed that C1q interacts directly with myelin associated glycoprotein (MAG) in myelin, resulting in reduced activation of growth inhibitory signaling in neurons. In agreement with a C1q-outgrowth-enhancing mechanism in which C1q binding to MAG reduces MAG signaling to neurons, complement C1q blocked both the growth inhibitory and repulsive turning effects of MAG in vitro. Furthermore, C1q KO mice demonstrated increased...Continue Reading

Citations

May 6, 2016·Frontiers in Cellular Neuroscience·M Akhtar AnwarAli H Eid
Dec 3, 2016·Journal of Neuroinflammation·Yiting LiuJeffrey L Bennett
Mar 14, 2017·International Journal of Molecular Sciences·Joseph BehnkeJanet Alder
Mar 30, 2017·Scientific Reports·Gary Hin-Fai YamJodhbir S Mehta
Sep 15, 2020·ELife·Mark Noble, Christoph Pröschel
Oct 12, 2017·Scientific Reports·Sheri L PetersonAileen J Anderson
Aug 18, 2017·Journal of Neurotrauma·Francesco RoselliMarkus Huber-Lang
Aug 1, 2018·Cell Death Discovery·S DanielC M McDowell
Mar 20, 2019·Frontiers in Immunology·Sarah M CarpaniniBryan Paul Morgan
Aug 4, 2020·Royal Society Open Science·Harry Ward, Steven J West
Nov 26, 2020·Annual Review of Pathology·Nicholas E PropsonHui Zheng
Oct 15, 2020·Clinical Oral Investigations·Madison BergmannImad About
Jun 19, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Xin-Qiang YaoJian-Ting Chen
Aug 20, 2021·The Journal of Biological Chemistry·Charles A WarwickYuriy M Usachev

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