The L1 cell adhesion molecule constrains dendritic spine density in pyramidal neurons of the mouse cerebral cortex

被引:4
|
作者
Murphy, Kelsey E. [1 ,2 ]
Wade, Sarah D. [1 ,2 ]
Sperringer, Justin E. [1 ,2 ]
Mohan, Vishwa [1 ,2 ]
Duncan, Bryce W. [1 ,2 ]
Zhang, Erin Y. Y. [1 ,2 ]
Pak, Yubin [1 ,2 ]
Lutz, David [3 ]
Schachner, Melitta [4 ,5 ]
Maness, Patricia F. [1 ,2 ]
机构
[1] Univ N Carolina, Dept Biochem & Biophys, Sch Med, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, Carolina Inst Dev Disabil, Sch Med, Chapel Hill, NC 27599 USA
[3] Ruhr Univ Bochum, Div Neuroanat & Mol Brain Res, Bochum, Germany
[4] Rutgers State Univ, Keck Ctr Collaborat Neurosci, Piscatawy, NJ USA
[5] Rutgers State Univ, Dept Cell Biol & Neurosci, Piscatawy, NJ USA
来源
FRONTIERS IN NEUROANATOMY | 2023年 / 17卷
基金
美国国家卫生研究院;
关键词
L1 cell adhesion molecule; ankyrin; dendritic spines; pyramidal neurons; cortical development; mouse models; X-LINKED HYDROCEPHALUS; MICE; AUTISM; TRANSMISSION; DYSGENESIS; MUTATIONS; NEOCORTEX; SYNAPSES; ABLATION; L1CAM;
D O I
10.3389/fnana.2023.1111525
中图分类号
R602 [外科病理学、解剖学]; R32 [人体形态学];
学科分类号
100101 ;
摘要
A novel function for the L1 cell adhesion molecule, which binds the actin adaptor protein Ankyrin was identified in constraining dendritic spine density on pyramidal neurons in the mouse neocortex. In an L1-null mouse mutant increased spine density was observed on apical but not basal dendrites of pyramidal neurons in diverse cortical areas (prefrontal cortex layer 2/3, motor cortex layer 5, visual cortex layer 4. The Ankyrin binding motif (FIGQY) in the L1 cytoplasmic domain was critical for spine regulation, as demonstrated by increased spine density and altered spine morphology in the prefrontal cortex of a mouse knock-in mutant (L1YH) harboring a tyrosine (Y) to histidine (H) mutation in the FIGQY motif, which disrupted L1-Ankyrin association. This mutation is a known variant in the human L1 syndrome of intellectual disability. L1 was localized by immunofluorescence staining to spine heads and dendrites of cortical pyramidal neurons. L1 coimmunoprecipitated with Ankyrin B (220 kDa isoform) from lysates of wild type but not L1YH forebrain. This study provides insight into the molecular mechanism of spine regulation and underscores the potential for this adhesion molecule to regulate cognitive and other L1-related functions that are abnormal in the L1 syndrome.
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页数:11
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