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A family of proteins implicated in axon guidance and outgrowth
C C Quinn1, G E Gray, S Hockfield
1Section of Neurobiology, Yale University School of Medicine, Cedar Street, SHM C-405, New Haven, Connecticut 06520-8001, USA.
Abstract:
Rapid progress in the identification and characterization of axon guidance molecules and their receptors has left the field poised to explore the intracellular mechanisms by which signals are transduced into growth cone responses. The TUC (TOAD/Ulip/CRMP) family of proteins has emerged as a strong candidate for a role in growth cone signaling. The TUC family members reach their highest expression levels in all neurons during their peak periods of axonal growth and are strongly down-regulated afterward. When axonal regrowth in the adult is triggered by axotomy, TUC-4 is reexpressed during the period of regrowth. Mutations in unc-33, a homologous nematode gene, lead to severe axon guidance errors in all neurons. Furthermore, the TUC family is required for the growth cone-collapsing activity of collapsin-1. An important role for the TUC family is also suggested by its high degree of interspecies amino acid sequence identity, with the rat TUC-2 protein showing 98% identity with its chick ortholog and 89% identity with its Xenopus ortholog. Information gained from the study of the TUC family will be of key importance in understanding how growth cones find their targets.
Insights
The TUC protein family is crucial for guiding neuron growth cones. Its expression and function are vital for axon guidance and regrowth, offering insights into neural development.
Area of Science:
- Neuroscience
- Molecular Biology
- Developmental Biology
Background:
- Axon guidance relies on intracellular signaling pathways.
- The TUC (TOAD/Ulip/CRMP) protein family is implicated in growth cone signaling.
- TUC proteins are highly expressed during axonal growth and reexpressed during adult axonal regrowth.
Purpose of the Study:
- To investigate the role of the TUC protein family in intracellular mechanisms of axon guidance.
- To understand the function of TUC proteins in growth cone responses to guidance cues.
Main Methods:
- Analysis of TUC protein expression patterns during axonal growth and regrowth.
- Examination of the effects of mutations in homologous genes (e.g., unc-33) on axon guidance.
- Assessing the requirement of the TUC family for growth cone-collapsing activities.
Main Results:
- TUC proteins show peak expression during axonal growth and are reexpressed during adult regrowth.
- Homologous gene mutations (unc-33) cause significant axon guidance errors.
- The TUC family is essential for the growth cone-collapsing effect of collapsin-1.
- High interspecies sequence identity suggests conserved function.
Conclusions:
- The TUC protein family plays a critical role in axon guidance and growth cone signaling.
- Understanding TUC proteins is key to deciphering how growth cones navigate to their targets.
- TUC proteins are important targets for understanding neural development and repair.