Role of cell adhesions in neural development: Difference between revisions

Revision as of 08:31, 13 May 2014

Revision as of 04:11, 24 July 2014

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===Integrin dependent migration===

Integrin dependent cell migration can be described as protein plaques that form the mechanical linkage between the intracellular and extracellular environments. One major components of this classification of cell migration, [[integrin]], is a trans-membrenal protein dimer, which binds ECM components on its external domains and [[actin]] cytoskeletal components on its intra-cellular domains. These adhesions couple forces between the intracellular and extracellular space through both actin retrograde flow mechanisms (which have been described as a molecular clutch), and through actin-myosin protein contraction machinery. It is thought that these adhesions are involved in mechanosensing, that is, they respond both physically and chemically when exposed to various physical environments.<ref name="urlMechanosensitive channels">{{cite web | url = http://www.ks.uiuc.edu/Research/MscLchannel/ | title = Mechanosensitive channels | author = Gullingsrud J, Sotomayor M | authorlink = | coauthors = | format = | work = | publisher = Theoretical and Computational Biophysics Group, Beckman Institute for Advanced Science and Technology: University of Illinois at Urbana-Champaign| pages = | language = | archiveurl = | archivedate = | quote = | accessdate = }}</ref>

==Adhesion-related mechanisms involved in neuronal tissue development==

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===Thy-1 adhesion protein===

Thy-1 (or [[thy-1|CD90.2]]) is a membrane bound [[glycoprotein]] that has been shown to be involved in the [[axon guidance]] pathway. This protein has been shown to be highly mobile, as it contains a [[Glycophosphatidylinositol|GPI]] membrane anchor. Although much of the details are elusive, it is known that thy-1 interacts with the protein dimer integrin found on [[astrocytes]], forming aggregates that can inhibit neurite outgrowth and extension. Thy-1 has also been shown to have involvement in the [[src (gene)|src]]-family kinase pathway.<ref>{{cite journal|last=Rege|first=Tanya|title=Thy-1, via its GPI anchor, modulates Src family kinase and focal adhesion kinase phosphorylation and subcellular localization, and fibroblast migration, in response to thrombospondin-1/hep I|journal=Chronology|year=2006|doi=10.1016/j.yexcr.2006.07.029}}</ref> This astrocyte-neuron feedback has been proposed as a mechanism involved in CNS tissue repair post-injury, as a down regulation of thy-1 may lead to enhanced neurite outgrowth. Additional research has shown that thy-1 expression in post natal humans is elevated for several weeks. This suggests that in addition to tissue repair, thy-1 might have roles in early CNS tissue development and organization.<ref>{{cite journal|last=Herrera-Molina|first=Rodrigo|coauthorsauthor2=et al |title=Astrocytic aVb3 Integrin Inhibits Neurite Outgrowth and Promotes Retraction of Neuronal Processes by Clustering Thy-1|journal=PLoS ONE|date=May 2012|volume=7|series=3|pages=e34295|doi=10.1371/journal.pone.0034295}}</ref><ref>{{cite journal|last=Barker|first=Thomas|title=Thy-1 regulates fibroblast focal adhesions, cytoskeletal organization and migration through modulation of p190 RhoGAP and Rho GTPase activity|journal=Experimental Cell Research|year=2004|issue=295|pages=488–496}}</ref>

===L1 family protein===

The [[L1 family]] of proteins are involved in neuronal migration, as well as in axon growth and proper synapse formation, and include L1CAM NrCAM and neurofascin. L1-Cell Adhesion Molecule (L1CAM) was first discovered to be important in neuron-related tissue development in the mid-1980s, and is a trans-membranal glycoprotein of approximately 200-220 kDa. On its extracellular ___domain, the L1CAM protein includes [[Immunoglobulin|IgG]]-like and [[fibronectin]]-III (FN-III) repeats which allow for interaction with integrins and ECM proteins. Similarly to integrin, F1CAM expresses domains intracellularly that interact with the actin cytoskeleton. Supporting the claim that L1-family proteins are involved in CNS development is the finding that L1CAM is highly expressed in neuronal tissue during its early stages of growth, especially at the ends of axons. Some areas of the brain, such as the hippocampus, have been found to highly express L1CAM into adulthood, though the exact reason for this has not been elucidated.

Due to its involvement in neuronal development and axon guidance, its has been proposed that L1CAM and L1-family proteins may be useful therapeutics to treat tissue damage in the CNS. Some have even proposed that L1CAM expression is elevated in vivo during tissue repair, which would support the notion that it yields benefit during CNS tissue repair.<ref>{{cite journal|last=Schafer|first=Michael|coauthorsauthor2=Michael Frotscher |title=Role of L1CAM for axon sprouting and branching|journal=Cell Tissue Res|date=February 2012|volume=349|pages=39–48|doi=10.1007/s00441-012-1345-4}}</ref>

===Mechanosensing in neurons===

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Several debilitating diseases are brought about from errors in neural development due in part to problems involving neural cell adhesions and adhesion mechanisms.

*CRASH syndrome (or L1 syndrome) is brought about by a mutation in the L1CAM gene on the x-[[chromosome]], resulting in a malfunctioning L1CAM protein. CRASH (acronym) syndrome include the conditions:<ref name="pmid8556302">{{cite journal |author=Fransen E, Lemmon V, Van Camp G, Vits L, Coucke P, Willems PJ |title=CRASH syndrome: clinical spectrum of corpus callosum hypoplasia, retardation, adducted thumbs, spastic paraparesis and hydrocephalus due to mutations in one single gene, L1 |journal=European Journal of Human Genetics |volume=3 |issue=5 |pages=273–84 |year=1995 |pmid=8556302 }}</ref><ref name="pmid7562969">{{cite journal |author=Ruiz JC, Cuppens H, Legius E, ''et al.''|title=Mutations in L1-CAM in two families with X linked complicated spastic paraplegia, MASA syndrome, and HSAS |journal=Journal of medical genetics |volume=32 |issue=7 |pages=549–52 |date=July 1995 |pmid=7562969 |pmc=1050549 |doi= 10.1136/jmg.32.7.549|url=}}</ref>

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