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rab-27 acts in an intestinal pathway to inhibit axon regeneration in C. elegans

Alexander T Lin-Moore1, Motunrayo J Oyeyemi2, Marc Hammarlund1,3

  • 1Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, United States of America.

Plos Genetics
|November 24, 2021
PubMed

Insights

The Rab GTPase rab-27 in the intestine inhibits axon regeneration in C. elegans. This study reveals long-distance signals from distal tissues regulate nerve repair.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Developmental Biology

Background:

  • Axon regeneration is crucial for restoring nervous system function after injury.
  • External factors from non-neuronal tissues regulate axon regeneration.
  • The existence of long-distance signals controlling regeneration has been unclear.

Purpose of the Study:

  • To investigate the role of long-distance signaling in axon regeneration.
  • To identify specific genes and pathways involved in regulating regeneration from distal tissues.

Main Methods:

  • Utilized the C. elegans model system to study GABAergic motor neuron regeneration.
  • Employed gene re-expression experiments in rab-27 mutant animals.
  • Performed genetic interaction studies.

Main Results:

  • The Rab GTPase rab-27, acting in the intestine, inhibits axon regeneration.
  • Re-expression of RAB-27 in the intestine rescues normal regeneration.
  • Components of an intestinal neuropeptide secretion pathway (NPDC1/cab-1, SNAP25/aex-4, KPC3/aex-5, NLP-40) also inhibit regeneration.
  • NPDC1/cab-1 and SNAP25/aex-4 genetically interact with rab-27.

Conclusions:

  • RAB-27-dependent neuropeptide secretion from the intestine inhibits axon regeneration.
  • Distal tissues act as potent extrinsic regulators of axon regeneration.

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