FICD activity and AMPylation remodelling modulate human neurogenesis

Posttranslational modification (PTM) of proteins represents an important cellular mechanism for controlling diverse functions such as signalling, localisation or protein-protein interactions1. AMPylation (also termed adenylylation) has recently been discovered as a prevalent PTM for regulating protein activity2. In human cells AMPylation has been exclusively studied with the FICD protein3–6. Here we investigate the role of AMPylation in human neurogenesis by introducing a cell-permeable propargyl adenosine pronucleotide probe to infiltrate cellular AMPylation pathways and report distinct modifications in intact cancer cell lines, human-derived stem cells, neural progenitor cells (NPCs), neurons and cerebral organoids (COs) via LC-MS/MS as well as imaging methods. A total of 162 AMP modified proteins were identified. FICD-dependent AMPylation remodelling accelerates differentiation of neural progenitor cells into mature neurons in COs, demonstrating a so far unknown trigger of human neurogenesis.

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A Role of CPEB1 in the Modulation of Proliferation and Neuronal Maturation of Rat Primary Neural Progenitor Cells

Neurochemical Research ◽

10.1007/s11064-013-1102-4 ◽

2013 ◽

Vol 38 (9) ◽

pp. 1960-1972 ◽

Cited By ~ 6

Author(s):

Ki Chan Kim ◽

Ji-Woon Kim ◽

Chang Soon Choi ◽

Sun Young Han ◽

Jae Hoon Cheong ◽

...

Keyword(s):

Progenitor Cells ◽

Neural Progenitor Cells ◽

Neural Progenitor ◽

Neuronal Maturation

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SEPT7 Interacts with KIF20A and Regulates the Proliferative State of Neural Progenitor Cells During Cortical Development

Cerebral Cortex ◽

10.1093/cercor/bhz292 ◽

2019 ◽

Vol 30 (5) ◽

pp. 3030-3043 ◽

Cited By ~ 2

Author(s):

Runxiang Qiu ◽

Qiu Runxiang ◽

Anqi Geng ◽

Jiancheng Liu ◽

C Wilson Xu ◽

...

Keyword(s):

Cell Division ◽

Progenitor Cells ◽

Neuronal Differentiation ◽

Cell Fate ◽

Neural Progenitor Cells ◽

Cortical Development ◽

Neural Progenitor ◽

Mammalian Brain ◽

Additional Cell ◽

A Cell

Abstract Balanced proliferation and differentiation of neural progenitor cells (NPCs) are critical for brain development, but how the process is regulated and what components of the cell division machinery is involved are not well understood. Here we report that SEPT7, a cell division regulator originally identified in Saccharomyces cerevisiae, interacts with KIF20A in the intercellular bridge of dividing NPCs and plays an essential role in maintaining the proliferative state of NPCs during cortical development. Knockdown of SEPT7 in NPCs results in displacement of KIF20A from the midbody and early neuronal differentiation. NPC-specific inducible knockout of Sept7 causes early cell cycle exit, precocious neuronal differentiation, and ventriculomegaly in the cortex, but surprisingly does not lead to noticeable cytokinesis defect. Our data uncover an interaction of SEPT7 and KIF20A during NPC divisions and demonstrate a crucial role of SEPT7 in cell fate determination. In addition, this study presents a functional approach for identifying additional cell fate regulators of the mammalian brain.

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Mammalian Fat and Dachsous cadherins regulate apical membrane organization in the embryonic cerebral cortex

The Journal of Cell Biology ◽

10.1083/jcb.200811030 ◽

2009 ◽

Vol 185 (6) ◽

pp. 959-967 ◽

Cited By ~ 51

Author(s):

Takashi Ishiuchi ◽

Kazuyo Misaki ◽

Shigenobu Yonemura ◽

Masatoshi Takeichi ◽

Takuji Tanoue

Keyword(s):

Cerebral Cortex ◽

Plasma Membrane ◽

Progenitor Cells ◽

Neural Progenitor Cells ◽

Apical Membrane ◽

Neural Progenitor ◽

Apical Plasma Membrane ◽

Cell Contact ◽

Membrane Organization ◽

A Cell

Compartmentalization of the plasma membrane in a cell is fundamental for its proper functions. In this study, we present evidence that mammalian Fat4 and Dachsous1 cadherins regulate the apical plasma membrane organization in the embryonic cerebral cortex. In neural progenitor cells of the cortex, Fat4 and Dachsous1 were concentrated together in a cell–cell contact area positioned more apically than the adherens junction (AJ). These molecules interacted in a heterophilic fashion, affecting their respective protein levels. We further found that Fat4 associated and colocalized with the Pals1 complex. Ultrastructurally, the apical junctions of the progenitor cells comprised the AJ and a stretch of plasma membrane apposition extending apically from the AJ, which positionally corresponded to the Fat4–Dachsous1-positive zone. Depletion of Fat4 or Pals1 abolished this membrane apposition. These results highlight the importance of the Fat4–Dachsous1–Pals1 complex in organizing the apical membrane architecture of neural progenitor cells.

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