Kalirin loss results in cortical morphological alterations

Zhong Xie; Michael E. Cahill; Peter Penzes

doi:10.1016/j.mcn.2009.09.006

Kalirin loss results in cortical morphological alterations

Zhong Xie, Michael E. Cahill, Peter Penzes^*

^*Corresponding author for this work

Neuroscience

Research output: Contribution to journal › Article › peer-review

48 Scopus citations

Abstract

Morphogenesis of pyramidal neuronal dendrites and spines is crucial for the formation and refinement of forebrain neuronal circuits underlying cognition. Aberrant dendrite and spine morphology is associated with neuropathological disorders. However, the molecular mechanisms controlling pyramidal neuronal dendrite and spine morphogenesis in vivo remain largely unknown. Kalirin is a brain-specific guanine-nucleotide exchange factor for Rho-like small GTPases, and an important regulator of spine morphogenesis in cultured neurons. Here we show that RNAi-dependent knockdown of kalirin in cultured neurons affected dendrite morphology. Cortical pyramidal neurons from KALRN-null mice showed reduced spine density and impaired activity-dependent spine plasticity; and they exhibited reduced complexity of dendritic trees. KALRN-null mice also displayed smaller neuronal cell bodies and reductions in the size of the cortex and cortical layers. These data demonstrate important roles for kalirin in the regulation of cortical structure, ultrastructure, and spine structural plasticity.

Original language	English (US)
Pages (from-to)	81-89
Number of pages	9
Journal	Molecular and Cellular Neuroscience
Volume	43
Issue number	1
DOIs	https://doi.org/10.1016/j.mcn.2009.09.006
State	Published - Jan 2010

Funding

We thank Dr. Richard L. Huganir (Johns Hopkins University) for the GluR1 polyclonal antibody; Dr. Gary G. Borisy and Dr. Shin-ichiro Kojima (Northwestern University) for the pGsuper plasmid and assistance with RNAi; and Kelly Jones and Igor Rafalovich for editing. This work was supported by grants from NIH-NIMH ( R01MH071316 ), National Alliance for Autism Research (NAAR), National Alliance for Research on Schizophrenia and Depression (NARSAD), and Alzheimer's Association (to P.P.), and training grants ( NINDS 5T32NS041234-08 ) to Z.X. and ( NIH 1F31AG031621-01A2 ) to M.E.C.

Keywords

Dendrites
Dendritic spine
KALRN
Knockout
Prefrontal cortex
Rac1
Small GTPase
Synaptic plasticity

ASJC Scopus subject areas

Cellular and Molecular Neuroscience
Molecular Biology
Cell Biology

Access to Document

10.1016/j.mcn.2009.09.006

Cite this

@article{f12e069bc47341ecbfc629840d34aea5,

title = "Kalirin loss results in cortical morphological alterations",

abstract = "Morphogenesis of pyramidal neuronal dendrites and spines is crucial for the formation and refinement of forebrain neuronal circuits underlying cognition. Aberrant dendrite and spine morphology is associated with neuropathological disorders. However, the molecular mechanisms controlling pyramidal neuronal dendrite and spine morphogenesis in vivo remain largely unknown. Kalirin is a brain-specific guanine-nucleotide exchange factor for Rho-like small GTPases, and an important regulator of spine morphogenesis in cultured neurons. Here we show that RNAi-dependent knockdown of kalirin in cultured neurons affected dendrite morphology. Cortical pyramidal neurons from KALRN-null mice showed reduced spine density and impaired activity-dependent spine plasticity; and they exhibited reduced complexity of dendritic trees. KALRN-null mice also displayed smaller neuronal cell bodies and reductions in the size of the cortex and cortical layers. These data demonstrate important roles for kalirin in the regulation of cortical structure, ultrastructure, and spine structural plasticity.",

keywords = "Dendrites, Dendritic spine, KALRN, Knockout, Prefrontal cortex, Rac1, Small GTPase, Synaptic plasticity",

author = "Zhong Xie and Cahill, {Michael E.} and Peter Penzes",

note = "Funding Information: We thank Dr. Richard L. Huganir (Johns Hopkins University) for the GluR1 polyclonal antibody; Dr. Gary G. Borisy and Dr. Shin-ichiro Kojima (Northwestern University) for the pGsuper plasmid and assistance with RNAi; and Kelly Jones and Igor Rafalovich for editing. This work was supported by grants from NIH-NIMH ( R01MH071316 ), National Alliance for Autism Research (NAAR), National Alliance for Research on Schizophrenia and Depression (NARSAD), and Alzheimer's Association (to P.P.), and training grants ( NINDS 5T32NS041234-08 ) to Z.X. and ( NIH 1F31AG031621-01A2 ) to M.E.C. ",

year = "2010",

month = jan,

doi = "10.1016/j.mcn.2009.09.006",

language = "English (US)",

volume = "43",

pages = "81--89",

journal = "Molecular and Cellular Neuroscience",

issn = "1044-7431",

publisher = "Academic Press Inc.",

number = "1",

}

TY - JOUR

T1 - Kalirin loss results in cortical morphological alterations

AU - Xie, Zhong

AU - Cahill, Michael E.

AU - Penzes, Peter

N1 - Funding Information: We thank Dr. Richard L. Huganir (Johns Hopkins University) for the GluR1 polyclonal antibody; Dr. Gary G. Borisy and Dr. Shin-ichiro Kojima (Northwestern University) for the pGsuper plasmid and assistance with RNAi; and Kelly Jones and Igor Rafalovich for editing. This work was supported by grants from NIH-NIMH ( R01MH071316 ), National Alliance for Autism Research (NAAR), National Alliance for Research on Schizophrenia and Depression (NARSAD), and Alzheimer's Association (to P.P.), and training grants ( NINDS 5T32NS041234-08 ) to Z.X. and ( NIH 1F31AG031621-01A2 ) to M.E.C.

PY - 2010/1

Y1 - 2010/1

N2 - Morphogenesis of pyramidal neuronal dendrites and spines is crucial for the formation and refinement of forebrain neuronal circuits underlying cognition. Aberrant dendrite and spine morphology is associated with neuropathological disorders. However, the molecular mechanisms controlling pyramidal neuronal dendrite and spine morphogenesis in vivo remain largely unknown. Kalirin is a brain-specific guanine-nucleotide exchange factor for Rho-like small GTPases, and an important regulator of spine morphogenesis in cultured neurons. Here we show that RNAi-dependent knockdown of kalirin in cultured neurons affected dendrite morphology. Cortical pyramidal neurons from KALRN-null mice showed reduced spine density and impaired activity-dependent spine plasticity; and they exhibited reduced complexity of dendritic trees. KALRN-null mice also displayed smaller neuronal cell bodies and reductions in the size of the cortex and cortical layers. These data demonstrate important roles for kalirin in the regulation of cortical structure, ultrastructure, and spine structural plasticity.

AB - Morphogenesis of pyramidal neuronal dendrites and spines is crucial for the formation and refinement of forebrain neuronal circuits underlying cognition. Aberrant dendrite and spine morphology is associated with neuropathological disorders. However, the molecular mechanisms controlling pyramidal neuronal dendrite and spine morphogenesis in vivo remain largely unknown. Kalirin is a brain-specific guanine-nucleotide exchange factor for Rho-like small GTPases, and an important regulator of spine morphogenesis in cultured neurons. Here we show that RNAi-dependent knockdown of kalirin in cultured neurons affected dendrite morphology. Cortical pyramidal neurons from KALRN-null mice showed reduced spine density and impaired activity-dependent spine plasticity; and they exhibited reduced complexity of dendritic trees. KALRN-null mice also displayed smaller neuronal cell bodies and reductions in the size of the cortex and cortical layers. These data demonstrate important roles for kalirin in the regulation of cortical structure, ultrastructure, and spine structural plasticity.

KW - Dendrites

KW - Dendritic spine

KW - KALRN

KW - Knockout

KW - Prefrontal cortex

KW - Rac1

KW - Small GTPase

KW - Synaptic plasticity

UR - http://www.scopus.com/inward/record.url?scp=72149094050&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=72149094050&partnerID=8YFLogxK

U2 - 10.1016/j.mcn.2009.09.006

DO - 10.1016/j.mcn.2009.09.006

M3 - Article

C2 - 19800004

AN - SCOPUS:72149094050

SN - 1044-7431

VL - 43

SP - 81

EP - 89

JO - Molecular and Cellular Neuroscience

JF - Molecular and Cellular Neuroscience

IS - 1

ER -

Kalirin loss results in cortical morphological alterations

Abstract

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this