한빛사논문
Bon Seong Goo1, Dong Jin Mun1, Seunghyun Kim1, Truong Thi My Nhung1, Su Been Lee 1, Youngsik Woo 1, Soo Jeong Kim1, Bo Kyoung Suh1, Sung Jin Park1,4, Hee-Eun Lee 1, Kunyou Park1, Hyunsoo Jang2, Jong-Cheol Rah3, Ki-Jun Yoon 2, Seung Tae Baek 1, Seung-Yeol Park 1 and Sang Ki Park 1
1Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
2Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.
3Korea Brain Research Institute, Daegu 41062, Republic of Korea.
4Present address: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Corresponding authors: Correspondence to Seung-Yeol Park or Sang Ki Park.
Abstract
Although large-scale genome-wide association studies (GWAS) have identified an association between MAD1L1 (Mitotic Arrest Deficient-1 Like 1) and the pathology of schizophrenia, the molecular mechanisms underlying this association remain unclear. In the present study, we aimed to address these mechanisms by examining the role of MAD1 (the gene product of MAD1L1) in key neurodevelopmental processes in mice and human organoids. Our findings indicated that MAD1 is highly expressed during active cortical development and that MAD1 deficiency leads to impairments in neuronal migration and neurite outgrowth. We also observed that MAD1 is localized to the Golgi apparatus and regulates vesicular trafficking from the Golgi apparatus to the plasma membrane, which is required for the growth and polarity of migrating neurons. In this process, MAD1 physically interacts and collaborates with the kinesin-like protein KIFC3 (kinesin family member C3) to regulate the morphology of the Golgi apparatus and neuronal polarity, thereby ensuring proper neuronal migration and differentiation. Consequently, our findings indicate that MAD1 is an essential regulator of neuronal development and that alterations in MAD1 may underlie schizophrenia pathobiology.
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