RESUMO
Regulation of microtubule dynamics is required to properly control various steps of neurodevelopment. In this study, we identified granule cell antiserum-positive 14 (Gcap14) as a microtubule plus-end-tracking protein and as a regulator of microtubule dynamics during neurodevelopment. Gcap14 knockout mice exhibited impaired cortical lamination. Gcap14 deficiency resulted in defective neuronal migration. Moreover, nuclear distribution element nudE-like 1 (Ndel1), an interacting partner of Gcap14, effectively corrected the downregulation of microtubule dynamics and the defects in neuronal migration caused by Gcap14 deficiency. Finally, we found that the Gcap14-Ndel1 complex participates in the functional link between microtubule and actin filament, thereby regulating their crosstalks in the growth cones of cortical neurons. Taken together, we propose that the Gcap14-Ndel1 complex is fundamental for cytoskeletal remodeling during neurodevelopmental processes such as neuronal processes elongation and neuronal migration.
Assuntos
Actinas , Proteínas Associadas aos Microtúbulos , Neurônios , Animais , Camundongos , Actinas/metabolismo , Movimento Celular/fisiologia , Camundongos Knockout , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Microtúbulos/metabolismo , Neuritos/metabolismo , Neurônios/metabolismoRESUMO
Lipids on the plasma membrane are not only components of the membrane biophysical structures but also regulators of receptor functions. Recently, the critical roles of lipid-protein interactions have been intensively highlighted. Epidermal growth factor receptor (EGFR) is one of the most extensively studied receptors exhibiting various lipid interactions, including interactions with phosphatidylcholine, phosphatidylserine, phosphatidylinositol phosphate, cholesterol, gangliosides, and palmitate. Here, we review recent findings on how direct interaction with these lipids regulates EGFR activation and signaling, providing unprecedented insight into the comprehensive roles of various lipids in the control of EGFR functions. Finally, the current limitations in investigating lipid-protein interactions and novel technologies to potentially overcome these limitations are discussed.