Unknown

Dataset Information

0

Disruption of the axon initial segment cytoskeleton is a new mechanism for neuronal injury.


ABSTRACT: Many factors contribute to nervous system dysfunction and failure to regenerate after injury or disease. Here, we describe a previously unrecognized mechanism for nervous system injury. We show that neuronal injury causes rapid, irreversible, and preferential proteolysis of the axon initial segment (AIS) cytoskeleton independently of cell death or axon degeneration, leading to loss of both ion channel clusters and neuronal polarity. Furthermore, we show this is caused by proteolysis of the AIS cytoskeletal proteins ankyrinG and betaIV spectrin by the calcium-dependent cysteine protease calpain. Importantly, calpain inhibition is sufficient to preserve the molecular organization of the AIS both in vitro and in vivo. We conclude that loss of AIS ion channel clusters and neuronal polarity are important contributors to neuronal dysfunction after injury, and that strategies to facilitate recovery must preserve or repair the AIS cytoskeleton.

SUBMITTER: Schafer DP 

PROVIDER: S-EPMC2801423 | biostudies-other | 2009 Oct

REPOSITORIES: biostudies-other

altmetric image

Publications

Disruption of the axon initial segment cytoskeleton is a new mechanism for neuronal injury.

Schafer Dorothy P DP   Jha Smita S   Liu Fudong F   Akella Trupti T   McCullough Louise D LD   Rasband Matthew N MN  

The Journal of neuroscience : the official journal of the Society for Neuroscience 20091001 42


Many factors contribute to nervous system dysfunction and failure to regenerate after injury or disease. Here, we describe a previously unrecognized mechanism for nervous system injury. We show that neuronal injury causes rapid, irreversible, and preferential proteolysis of the axon initial segment (AIS) cytoskeleton independently of cell death or axon degeneration, leading to loss of both ion channel clusters and neuronal polarity. Furthermore, we show this is caused by proteolysis of the AIS c  ...[more]

Similar Datasets

| S-EPMC7031317 | biostudies-literature
| S-EPMC9433327 | biostudies-literature
| S-EPMC3987141 | biostudies-literature
| S-EPMC5823762 | biostudies-literature
| S-EPMC3482160 | biostudies-literature
| S-EPMC3196626 | biostudies-literature
| S-EPMC3361702 | biostudies-literature
| S-EPMC5263140 | biostudies-literature
| S-EPMC3531813 | biostudies-literature
| S-EPMC4673506 | biostudies-literature