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Microtubule Associated Proteins (MAPs)01:42

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Microtubule function and architecture are regulated by an array of specialized proteins called microtubule-associated proteins or MAPs. These proteins are widespread across different organisms and have conserved protein motifs, like the multi-TOG domain for tubulin binding found in the CLASP family of MAPs. Some MAPs are lineage-specific based on their conserved domains. Their functions depend upon the cytoskeletal architecture and cell type they are located within. In-plant cells, a specific...
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Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated...
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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
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Complex microtubule structures are present in resting cells and in dividing cells. In resting cells, they are responsible for maintaining the cellular architecture, tracks for intracellular transport, positioning of organelles, assembly of cilia and flagella. They mediate the bipolar spindle assembly for chromosomal segregation and positioning of the cell division plate in dividing cells. The formation of microtubule complex structures depends on the cell type, cell stage, and cell function.
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Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
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More than a marker: potential pathogenic functions of MAP2.

Rebecca A DeGiosio1, Melanie J Grubisha1, Matthew L MacDonald1

  • 1Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, United States.

Frontiers in Molecular Neuroscience
|October 3, 2022
PubMed
Summary

Microtubule-associated protein 2 (MAP2) is crucial for neuronal structure and function. Its dysregulation is implicated in various brain disorders, suggesting a new class of diseases termed "MAP2opathies".

Keywords:
MAP2cytoskeletonneurodegenerationneurodevelopmentpsychiatric disorder

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Microtubule-associated protein 2 (MAP2) is a key cytoskeletal regulator in neuronal dendrites.
  • MAP2 influences microtubule dynamics, neurite outgrowth, and synaptic functions, similar to MAP Tau.
  • While Tau pathology is well-studied, MAP2 dysregulation in neurodegenerative and neuropsychiatric disorders remains underexplored.

Purpose of the Study:

  • To review the structure and functions of MAP2.
  • To explore mechanisms of MAP2 regulation, including post-translational modifications.
  • To assess evidence of MAP2 dysregulation in brain disorders and propose its contribution to disease phenotypes.

Main Methods:

  • Literature review of MAP2 structure, function, and regulation.
  • Analysis of existing immunohistochemical and proteomic data on MAP2 in brain disorders.
  • Conceptualization of
  • MAP2opathy
  • based on proposed pathogenic pathways.

Main Results:

  • MAP2 plays vital roles in neurite outgrowth, synaptic plasticity, and protein homeostasis.
  • Alterations in MAP2 expression, splicing, and stability are observed across diverse neurological and psychiatric conditions.
  • Post-translational modifications represent a significant regulatory mechanism for MAP2 function.

Conclusions:

  • MAP2 dysregulation is a potential common pathogenic mechanism in multiple brain disorders.
  • The concept of
  • MAP2opathy
  • offers a novel framework for understanding these conditions.
  • Further research into MAP2's role could reveal new therapeutic targets for neurological and psychiatric diseases.