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Molecular and cellular neurosciences v.84, 2017년, pp.29 - 35   SCI SCIE SCOPUS
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How does calcium interact with the cytoskeleton to regulate growth cone motility during axon pathfinding?

Gasperini, Robert J. (School of Medicine, University of Tasmania, Hobart, Tasmania 7001, Australia ) ; Pavez, Macarena (School of Medicine, University of Tasmania, Hobart, Tasmania 7001, Australia ) ; Thompson, Adrian C. (School of Medicine, University of Tasmania, Hobart, Tasmania 7001, Australia ) ; Mitchell, Camilla B. (Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania 7001, Australia ) ; Hardy, Holly (University of Exeter Medical School, Wellcome Wolfson Centre for Medical Research, Exeter EX2 5DW, United Kingdom ) ; Young, Kaylene M. (Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania 7001, Australia ) ; Chilton, John K. (University of Exeter Medical School, Wellcome Wolfson Centre for Medical Research, Exeter EX2 5DW, United Kingdom ) ; Foa, Lisa (School of Medicine, University of Tasmania, Hobart, Tasmania 7001, Australia ) ;
  • 초록  

    Abstract The precision with which neurons form connections is crucial for the normal development and function of the nervous system. The development of neuronal circuitry in the nervous system is accomplished by axon pathfinding: a process where growth cones guide axons through the embryonic environment to connect with their appropriate synaptic partners to form functional circuits. Despite intense efforts over many years to understand how this process is regulated, the complete repertoire of molecular mechanisms that govern the growth cone cytoskeleton and hence motility, remain unresolved. A central tenet in the axon guidance field is that calcium signals regulate growth cone behaviours such as extension, turning and pausing by regulating rearrangements of the growth cone cytoskeleton. Here, we provide evidence that not only the amplitude of a calcium signal is critical for growth cone motility but also the source of calcium mobilisation. We provide an example of this idea by demonstrating that manipulation of calcium signalling via L-type voltage gated calcium channels can perturb sensory neuron motility towards a source of netrin-1. Understanding how calcium signals can be transduced to initiate cytoskeletal changes represents a significant gap in our current knowledge of the mechanisms that govern axon guidance, and consequently the formation of functional neural circuits in the developing nervous system. Highlights Calcium signaling regulates the cytoskeleton to control growth cone motility during axon guidance. The source, amplitude and spatial regulation of calcium signals are thought to regulate the cytoskeleton at the growth cone. Calcium-activated phosphorylation is the key signaling mechanism that links calcium and the growth cone cytoskeleton. Direct links between the endoplasmic reticulum and the cytoskeleton are implicated in growth cone motility.


  • 주제어

    Growth cone .   Calcium .   Axon guidance .   Cytoskeleton .   Endoplasmic reticulum (ER) .   Microtubules .   Actin.  

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