Regulation of autophagy by inhibitory CSPG interactions with receptor PTPσ and its impact on plasticity and regeneration after spinal cord injury

TY - JOUR

T1 - Regulation of autophagy by inhibitory CSPG interactions with receptor PTPσ and its impact on plasticity and regeneration after spinal cord injury

AU - Warren, Philippa

AU - Tran, Amanda

AU - Silver, Jerry

PY - 2020/6

Y1 - 2020/6

N2 - Chondroitin sulfate proteoglycans (CSPGs), extracellular matrix molecules that increase dramatically following a variety of CNS injuries or diseases, have long been known for their potent capacity to curtail cell migrations as well as axon regeneration and sprouting. The inhibition can be conferred through binding to their major cognate receptor, Protein Tyrosine Phosphatase Sigma (PTPσ). However, the precise mechanisms downstream of receptor binding that mediate growth inhibition have remained elusive. Recently, CSPGs/PTPσ interactions were found to regulate autophagic flux at the axon growth cone by dampening the autophagosome-lysosomal fusion step. Because of the intense interest in autophagic phenomena in the regulation of a wide variety of critical cellular functions, we summarize here what is currently known about dysregulation of autophagy following spinal cord injury, and highlight this critical new mechanism underlying axon regeneration failure. Furthermore, we review how CSPGs/PTPσ interactions influence plasticity through autophagic regulation and how PTPσ serves as a switch to execute either axon outgrowth or synaptogenesis. This has exciting implications for the role CSPGs play not only in axon regeneration failure after spinal cord injury, but also in neurodegenerative diseases where, again, inhibitory CSPGs are upregulated.

AB - Chondroitin sulfate proteoglycans (CSPGs), extracellular matrix molecules that increase dramatically following a variety of CNS injuries or diseases, have long been known for their potent capacity to curtail cell migrations as well as axon regeneration and sprouting. The inhibition can be conferred through binding to their major cognate receptor, Protein Tyrosine Phosphatase Sigma (PTPσ). However, the precise mechanisms downstream of receptor binding that mediate growth inhibition have remained elusive. Recently, CSPGs/PTPσ interactions were found to regulate autophagic flux at the axon growth cone by dampening the autophagosome-lysosomal fusion step. Because of the intense interest in autophagic phenomena in the regulation of a wide variety of critical cellular functions, we summarize here what is currently known about dysregulation of autophagy following spinal cord injury, and highlight this critical new mechanism underlying axon regeneration failure. Furthermore, we review how CSPGs/PTPσ interactions influence plasticity through autophagic regulation and how PTPσ serves as a switch to execute either axon outgrowth or synaptogenesis. This has exciting implications for the role CSPGs play not only in axon regeneration failure after spinal cord injury, but also in neurodegenerative diseases where, again, inhibitory CSPGs are upregulated.

KW - Autophagic flux

KW - Autophagy

KW - Axon regeneration

KW - Axonal dystrophy

KW - CSPGs

KW - Growth cone

KW - Lysosome

KW - Neural plasticity

KW - Neurodegeneration

KW - PTPσ

KW - Spinal cord injury

KW - Synaptogenesis

UR - http://www.scopus.com/inward/record.url?scp=85081019331&partnerID=8YFLogxK

U2 - 10.1016/j.expneurol.2020.113276

DO - 10.1016/j.expneurol.2020.113276

M3 - Review article

SN - 0014-4886

VL - 328

JO - Experimental Neurology

JF - Experimental Neurology

M1 - 113276

ER -