Autism and intellectual disability-associated KIRREL3 interacts with neuronal proteins MAP1B and MYO16 with potential roles in neurodevelopment

Ying F. Liu, Sarah M. Sowell, Yue Luo, Alka Chaubey, Richard S. Cameron, Hyung Goo Kim, Anand K. Srivastava

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Cell-adhesion molecules of the immunoglobulin superfamily play critical roles in brain development, as well as in maintaining synaptic plasticity, the dysfunction of which is known to cause cognitive impairment. Recently dysfunction of KIRREL3, a synaptic molecule of the immunoglobulin superfamily, has been implicated in several neurodevelopmental conditions including intellectual disability, autism spectrum disorder, and in the neurocognitive delay associated with Jacobsen syndrome. However, the molecular mechanisms of its physiological actions remain largely unknown. Using a yeast two-hybrid screen, we found that the KIRREL3 extracellular domain interacts with brain expressed proteins MAP1B and MYO16 and its intracellular domain can potentially interact with ATP1B1, UFC1, and SHMT2. The interactions were confirmed by co-immunoprecipitation and colocalization analyses of proteins expressed in human embryonic kidney cells, mouse neuronal cells, and rat primary neuronal cells. Furthermore, we show KIRREL3 colocalization with the marker for the Golgi apparatus and synaptic vesicles. Previously, we have shown that KIRREL3 interacts with the X-linked intellectual disability associated synaptic scaffolding protein CASK through its cytoplasmic domain. In addition, we found a genomic deletion encompassing MAP1B in one patient with intellectual disability, microcephaly and seizures and deletions encompassing MYO16 in two unrelated patients with intellectual disability, autism and microcephaly. MAP1B has been previously implicated in synaptogenesis and is involved in the development of the actin-based membrane skeleton. MYO16 is expressed in hippocampal neurons and also indirectly affects actin cytoskeleton through its interaction with WAVE1 complex. We speculate KIRREL3 interacting proteins are potential candidates for intellectual disability and autism spectrum disorder. Moreover, our findings provide further insight into understanding the molecular mechanisms underlying the physiological action of KIRREL3 and its role in neurodevelopment.

Original languageEnglish (US)
Article numbere0123106
JournalPLoS One
Volume10
Issue number4
DOIs
StatePublished - Apr 22 2015

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neurodevelopment
Autistic Disorder
Intellectual Disability
neurons
immunoglobulins
Microcephaly
scaffolding proteins
brain
Immunoglobulins
Actins
Brain
Proteins
proteins
Jacobsen Distal 11q Deletion Syndrome
kidney cells
seizures
Golgi apparatus
microfilaments
cell adhesion
actin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Autism and intellectual disability-associated KIRREL3 interacts with neuronal proteins MAP1B and MYO16 with potential roles in neurodevelopment. / Liu, Ying F.; Sowell, Sarah M.; Luo, Yue; Chaubey, Alka; Cameron, Richard S.; Kim, Hyung Goo; Srivastava, Anand K.

In: PLoS One, Vol. 10, No. 4, e0123106, 22.04.2015.

Research output: Contribution to journalArticle

Liu, Ying F. ; Sowell, Sarah M. ; Luo, Yue ; Chaubey, Alka ; Cameron, Richard S. ; Kim, Hyung Goo ; Srivastava, Anand K. / Autism and intellectual disability-associated KIRREL3 interacts with neuronal proteins MAP1B and MYO16 with potential roles in neurodevelopment. In: PLoS One. 2015 ; Vol. 10, No. 4.
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