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Merck
  • Regional heterogeneity of astrocyte morphogenesis dictated by the formin protein, Daam2, modifies circuit function.

Regional heterogeneity of astrocyte morphogenesis dictated by the formin protein, Daam2, modifies circuit function.

EMBO reports (2021-10-12)
Juyeon Jo, Junsung Woo, Carlo D Cristobal, Jong Min Choi, Chih-Yen Wang, Qi Ye, Joshua A Smith, Kevin Ung, Gary Liu, Diego Cortes, Sung Yun Jung, Benjamin R Arenkiel, Hyun Kyoung Lee
摘要

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.

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Sigma-Aldrich
泰莫西芬, ≥99%
Sigma-Aldrich
单克隆抗-FLAG® M2 小鼠抗, 1 mg/mL, clone M2, affinity isolated antibody, buffered aqueous solution (50% glycerol, 10 mM sodium phosphate, and 150 mM NaCl, pH 7.4)
Sigma-Aldrich
抗NeuN抗体,克隆A60, clone A60, Chemicon®, from mouse
Sigma-Aldrich
Monoclonal Anti-SLC4A4 antibody produced in mouse, clone 1G2, purified immunoglobulin, buffered aqueous solution