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Cited by 37Autism Spectrum Disorder ResearchGenetics and Neurodevelopmental DisordersCellular transport and secretion

Neuron Membrane Trafficking and Protein Kinases Involved in Autism and ADHD

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Kitagishi, Yasuko, Minami, Akari, Nakanishi, Atsuko, Ogura, Yasunori, Matsuda, Satoru·2015·International Journal of Molecular Sciences
DOI 10.3390/ijms16023095PMC PMC4346882
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Abstract

A brain-enriched multi-domain scaffolding protein, neurobeachin has been identified as a candidate gene for autism patients. Mutations in the synaptic adhesion protein cell adhesion molecule 1 (CADM1) are also associated with autism spectrum disorder, a neurodevelopmental disorder of uncertain molecular origin. Potential roles of neurobeachin and CADM1 have been suggested to a function of vesicle transport in endosomal trafficking. It seems that protein kinase B (AKT) and cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) have key roles in the neuron membrane trafficking involved in the pathogenesis of autism. Attention deficit hyperactivity disorder (ADHD) is documented to dopaminergic insufficiencies, which is attributed to synaptic dysfunction of dopamine transporter (DAT). AKT is also essential for the DAT cell-surface redistribution. In the present paper, we summarize and discuss the importance of several protein kinases that regulate the membrane trafficking involved in autism and ADHD, suggesting new targets for therapeutic intervention.

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  • PKC might induce p38 MAPK-mediated inactivation of AKTs, proteins essential for DAT cell surface redistribution due to AKT induction of actin reorganization, regulating the dopamine efflux impaired in ADHD.

    “In addition, PKC might induce p38 MAPK-mediated inactivation of AKTs [184, 185], proteins essential for DAT cell surface redistribution due to AKT induction of actin reorganization, regulating the dopamine efflux impaired in ADHD [186].”

    From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [186]

    Section 5 says AKT induces actin reorganization, is essential for DAT cell-surface redistribution, and may help regulate amphetamine-induced dopamine efflux through DAT. Section 4 links DAT to dopaminergic dysfunction in ADHD. The paper does not establish that actin reorganization causes DAT redistribution or that dopamine efflux itself is impaired in ADHD; the PKC–p38 MAPK clause is attached to other citations. (LLM, conf=0.82)

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Cited by

Sorted by citations

Authors
Kitagishi, Y., Minami, A., Nakanishi, A., Ogura, Y., & Matsuda, S.
Affiliations
Nara Women's University (JP)
Corresponding author
Matsuda, Satoru
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2015-01-30
Volume
16
Issue
2
Pages
3095-3115
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms16023095
PMC
PMC4346882
OpenAlex
W2053366935
Cited by
37
References
4
Citations by year
2026: 2 · 2025: 3 · 2024: 2 · 2023: 2 · 2022: 6 · 2021: 5 · 2020: 5 · 2019: 1 · 2018: 1 · 2017: 5 · 2016: 4 · 2015: 1
FWCI
0.36
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (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)
Funders
Japan Society for the Promotion of Science (24240098, 12035, 25560050)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
NBEA, CADM1, autism spectrum disorder, attention deficit hyperactivity disorder, protein kinases, Akt, pKa, vesicle trafficking, endosomal trafficking, dopamine transporter, synaptic dysfunction, therapeutic target
MeSH terms
Cell Adhesion Molecule-1, Attention Deficit Disorder with Hyperactivity, Autistic Disorder, Humans, Immunoglobulins, Neurons, Signal Transduction, Cell Adhesion Molecules, Protein Serine-Threonine Kinases, Cyclic AMP-Dependent Protein Kinases, Protein Transport, Dopamine Plasma Membrane Transport Proteins

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