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Baylor College of Medicine, Texas Children’s Hospital

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EMBO Rep., 11 October 2021, e53200 | https://doi.org/10.15252/embr.202153200 Regional heterogeneity of astrocyte morphogenesis dictated by the formin protein, Daam2, modifies circuit function

Juyeon Jo^1,2, Junsung Woo³, Carlo D Cristobal^2,4, Jong Min Choi⁵, Chih-Yen Wang^1,2, Qi Ye^1,2, Joshua A Smith^1,2, Kevin Ung^2,6, Gary Liu^2,6, Diego Cortes^1,2, Sung Yun Jung⁵, Benjamin R Arenkiel^2,6,7 and Hyun Kyoung Lee^*,1,2,4,6,7

¹Department of Pediatrics, Section of Neurology, Baylor College of Medicine, Houston, TX, USA
²Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX, USA
³Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA
⁴Program in Integrative Molecular and Biomedical Sciences, Baylor College of Medicine, Houston, TX, USA
⁵Center for Molecular Discovery, Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, USA
⁶Program in Developmental Biology, Baylor College of Medicine, Houston, TX, USA
⁷Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA

^*Corresponding author.

Abstract

Astrocytes display extraordinary morphological complexity that is essential to support brain circuit development and function. Formin proteins are key regulators of the cytoskeleton; however, their role in astrocyte morphogenesis across diverse brain regions and neural circuits is unknown. Here, we show that loss of the formin protein Daam2 in astrocytes increases morphological complexity in the cortex and olfactory bulb, but elicits opposing effects on astrocytic calcium dynamics. These differential physiological effects result in increased excitatory synaptic activity in the cortex and increased inhibitory synaptic activity in the olfactory bulb, leading to altered olfactory behaviors. Proteomic profiling and immunoprecipitation experiments identify Slc4a4 as a binding partner of Daam2 in the cortex, and combined deletion of Daam2 and Slc4a4 restores the morphological alterations seen in Daam2 mutants. Our results reveal new mechanisms regulating astrocyte morphology and show that congruent changes in astrocyte morphology can differentially influence circuit function.

Keywords : astrocyte; circuit; Daam2; heterogeneity; morphology

논문정보

형식Research article
게재일2021년 10월 (BRIC 등록일 2021-10-18)
연구진국외 연구진
분야 의약학 > 신경의학

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