Neuron membrane trafficking and protein kinases involved in autism and ADHD

Int J Mol Sci. 2015 Jan 30;16(2):3095-115. doi: 10.3390/ijms16023095.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Attention Deficit Disorder with Hyperactivity / metabolism
  • Attention Deficit Disorder with Hyperactivity / pathology*
  • Autistic Disorder / metabolism
  • Autistic Disorder / pathology*
  • Cell Adhesion Molecule-1
  • Cell Adhesion Molecules / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Humans
  • Immunoglobulins / metabolism
  • Neurons / metabolism*
  • Protein Serine-Threonine Kinases / metabolism
  • Protein Transport
  • Signal Transduction

Substances

  • CADM1 protein, human
  • Cell Adhesion Molecule-1
  • Cell Adhesion Molecules
  • Dopamine Plasma Membrane Transport Proteins
  • Immunoglobulins
  • Protein Serine-Threonine Kinases
  • Cyclic AMP-Dependent Protein Kinases