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Cited by 201Microtubule and mitosis dynamicsGenetics and Neurodevelopmental DisordersNeurogenesis and neuroplasticity mechanisms

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The Role of the Microtubule Cytoskeleton in Neurodevelopmental Disorders

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Lasser, Micaela, Tiber, Jessica, Lowery, Laura Anne·2018·Frontiers in Cellular Neuroscience
DOI 10.3389/fncel.2018.00165PMC PMC6010848
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Abstract

Neurons depend on the highly dynamic microtubule (MT) cytoskeleton for many different processes during early embryonic development including cell division and migration, intracellular trafficking and signal transduction, as well as proper axon guidance and synapse formation. The coordination and support from MTs is crucial for newly formed neurons to migrate appropriately in order to establish neural connections. Once connections are made, MTs provide structural integrity and support to maintain neural connectivity throughout development. Abnormalities in neural migration and connectivity due to genetic mutations of MT-associated proteins can lead to detrimental developmental defects. Growing evidence suggests that these mutations are associated with many different neurodevelopmental disorders, including intellectual disabilities (ID) and autism spectrum disorders (ASD). In this review article, we highlight the crucial role of the MT cytoskeleton in the context of neurodevelopment and summarize genetic mutations of various MT related proteins that may underlie or contribute to neurodevelopmental disorders.

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Figure 1 Microtubule (MT) basics. MTs are linear structures comprised of α-tubulin and β-tubulin heterodimers. MTs are extremely dynamic, existing in either a growing state (polymerization) or shrinking state (depolymerization), and can rapidly switch from growth to shrinkage (catastrophe) or from shrinkage to growth (rescue). Addition of new GTP-bound heterodimers occurs at the MT plus end during polymerization. Shortly thereafter, the tubulin subunits hydrolyze their bound GTP to GDP. When the addition of GTP-bound heterodimers slows and the MT lattice is composed of predominantly GDP-tubulin, the protofilaments splay apart and the MT depolymerizes.
Figure 1 Microtubule (MT) basics. MTs are linear structures comprised of α-tubulin and β-tubulin heterodimers. MTs are extremely dynamic, existing in either a growing state (polymerization) or shrinking state (depolymerization), and can rapidly switch from growth to shrinkage (catastrophe) or from shrinkage to growth (rescue). Addition of new GTP-bound heterodimers occurs at the MT plus end during polymerization. Shortly thereafter, the tubulin subunits hydrolyze their bound GTP to GDP. When the addition of GTP-bound heterodimers slows and the MT lattice is composed of predominantly GDP-tubulin, the protofilaments splay apart and the MT depolymerizes.CC BY · PubMed Central
Figure 2 MT organization and MT-associated proteins (MAPs) in axons and dendrites. In axons, MTs form stable, polarized bundles, which provide structural integrity and serve as tracks to guide MT-dependent motor proteins. Axonal MTs are stabilized by several MAPs including Tau, MAP1B and DCX. The growth cone contains an array of both stable and dynamic MTs, which prompt growth cone advancement and turning. Various +TIPs accumulate at the growing MT plus ends in the growth cone, where they regulate MT dynamics during axon outgrowth and guidance. MTs of mixed polarity are located within dendrites where MAP1A and MAP2 aid in MT stabilization. The MT-severing proteins, katanin and spastin, are critical for reorganizing the MT network in both axons and dendrites.
Figure 2 MT organization and MT-associated proteins (MAPs) in axons and dendrites. In axons, MTs form stable, polarized bundles, which provide structural integrity and serve as tracks to guide MT-dependent motor proteins. Axonal MTs are stabilized by several MAPs including Tau, MAP1B and DCX. The growth cone contains an array of both stable and dynamic MTs, which prompt growth cone advancement and turning. Various +TIPs accumulate at the growing MT plus ends in the growth cone, where they regulate MT dynamics during axon outgrowth and guidance. MTs of mixed polarity are located within dendrites where MAP1A and MAP2 aid in MT stabilization. The MT-severing proteins, katanin and spastin, are critical for reorganizing the MT network in both axons and dendrites.CC BY · PubMed Central

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Metadata

Authors
Lasser, M., Tiber, J., & Lowery, L. A.
Affiliations
Boston College (US)
Corresponding author
Lowery, Laura Anne
ORCID
Venue
Frontiers in Cellular Neuroscience
Publisher
Frontiers Media SA
Published
2018-06-14
Volume
12
Pages
165-165
ISSN
1662-5102 (ISSN-L)
DOI
10.3389/fncel.2018.00165
PMC
PMC6010848
OpenAlex
W2806503585
Cited by
201
References
219
Citations by year
2026: 15 · 2025: 22 · 2024: 24 · 2023: 30 · 2022: 32 · 2021: 35 · 2020: 29 · 2019: 12 · 2018: 2
FWCI
2.18
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institutes of Health (R01 MH109651, R01 GM121907)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
microtubule cytoskeleton, neurodevelopmental disorders, neuronal migration, intellectual disability, autism spectrum disorder, genetic mutations, axon guidance, synaptogenesis, neuronal connectivity, intracellular trafficking

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