Protein–Protein interactions, cytoskeletal regulation and neuronal migration

  title={Protein–Protein interactions, cytoskeletal regulation and neuronal migration},
  author={Yuanyi Feng and Christopher A. Walsh},
  journal={Nature Reviews Neuroscience},
Neuronal migration, like the migration of many cell types, requires an extensive rearrangement of cell shape, mediated by changes in the cytoskeleton. The genetic analysis of human brain malformations has identified several biochemical players in this process, including doublecortin (DCX) and LIS1, mutations of which cause a profound migratory disturbance known as lissencephaly ('smooth brain') in humans. Studies in mice have identified additional molecules such as Cdk5, P35, Reelin, Disabled… 

Cytoskeletal-associated proteins in the migration of cortical neurons.

This work states that disruption during development results in the ectopic placement of neurons in the cortex, and reviews key cytoskeletal events and the critical cytOSkeletal-associated proteins involved in cortical neuronal migration.

Distinct Features of Doublecortin as a Marker of Neuronal Migration and Its Implications in Cancer Cell Mobility

Current knowledge about Doublecortin (DCX), an essential factor in neurogenesis and mutations in this protein impairs neuronal migration, is summarized and an overview of its role in cancer cells is presented.

Disregulated RhoGTPases and Actin Cytoskeleton Contribute to the Migration Defect in Lis1-Deficient Neurons

Data indicate a previously unrecognized role for Lis1 protein in neuronal motility by promoting actin polymerization through the regulation of Rho GTPase activity.

DCX, a new mediator of the JNK pathway

It is demonstrated that DCX is a substrate of JNK and interacts with both c‐Jun N‐terminal kinase (JNK) and JNK interacting protein (JIP), and the localization of this signaling module in the developing brain suggests its functionality in migrating neurons.

A role of MAP1B in Reelin-dependent neuronal migration.

It is shown that Reelin can induce mode I MAP1B phosphorylation, both in vivo and in vitro, through gsk3 and cdk5 activation, and proposed that this could correlate with its function in neuronal migration.

Phosphorylation of Doublecortin by Protein Kinase A Orchestrates Microtubule and Actin Dynamics to Promote Neuronal Progenitor Cell Migration*

The data reveal a dual reciprocal role for DCX phosphorylation in the regulation of microtubule and actin dynamics that is indispensable for proper brain lamination.

Brain Malformations Associated with Cell Migration

  • I. NasrallahJ. Golden
  • Biology
    Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society
  • 2006
1 specific aspect of cerebral cortical development, cell migration, is focused on to explore the understanding of the molecular and cellular events that govern this aspect of development and to understand the functional consequences of disruptions in cell migration.

The role of the ezrin-radixin-moesin (ERM) proteins in development and post-injury responses of central nervous system neurons

Investigation of ERM protein function in CNS neurons, both during development and regeneration, shows that common mechanisms are required for developmental and regenerative nervous system growth, which is important or uncovering potential mechanisms of regenerative growth, and identifying therapeutic targets for encouraging post-injury regeneration.

The in vivo roles of STEF/Tiam1, Rac1 and JNK in cortical neuronal migration

Interestingly, distinct morphological phenotypes were observed; suppression of Rac1 activity caused loss of the leading process, whereas repression of JNK activity did not, suggesting the complexity of the signaling cascade, and provide important clues for understanding the intracellullar signaling machinery for cortical neuronal migration.



Reduction of microtubule catastrophe events by LIS1, platelet‐activating factor acetylhydrolase subunit

The new findings show that LIS1 is a protein exhibiting several cellular interactions, and the interaction with the cytoskeleton may prove to be the mode of transducing a signal generated by platelet‐activating factor.

Central nervous system neuronal migration.

  • M. Hatten
  • Biology
    Annual review of neuroscience
  • 1999
Molecular analysis of the genes that mark stages of secondary neurogenesis show similar expression patterns of a number of genes, so these three regions may have genetic pathways in common and be considered for human brain malformations and neurological mutant mice.

Regulation of cytoplasmic dynein behaviour and microtubule organization by mammalian Lis1

The results indicate that abundance of Lis1 in neurons may stimulate specific dynein functions that function in neuronal migration and axon growth.

Mouse disabled (mDab1): a Src binding protein implicated in neuronal development

The properties of mDab1 and genetic analysis of Dab in Drosophila suggest that these molecules function in key signal transduction pathways involved in the formation of neural networks.

Motility and cytoskeletal organization of migrating cerebellar granule neurons

  • RJ RivasME Hatten
  • Biology
    The Journal of neuroscience : the official journal of the Society for Neuroscience
  • 1995
The motility of the migratory leading process and cytoskeletal-based mechanisms of locomotion of early postnatal mouse cerebellar granule neurons in vitro were examined and involvement of actin subunit assembly in neuronal migration was suggested.