Ttyh1 regulates embryonic neural stem cell properties by enhancing the Notch signaling pathway. 2018

Juwan Kim, and Dasol Han, and Sung-Hyun Byun, and Mookwang Kwon, and Jae Youl Cho, and Samuel J Pleasure, and Keejung Yoon
College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, South Korea.

Despite growing evidence linking Drosophila melanogaster tweety-homologue 1 (Ttyh1) to normal mammalian brain development and cell proliferation, its exact role has not yet been determined. Here, we show that Ttyh1 is required for the maintenance of neural stem cell (NSC) properties as assessed by neurosphere formation and in vivo analyses of cell localization after in utero electroporation. We find that enhanced Ttyh1-dependent stemness of NSCs is caused by enhanced γ-secretase activity resulting in increased levels of Notch intracellular domain (NICD) production and activation of Notch targets. This is a unique function of Ttyh1 among all other Ttyh family members. Molecular analyses revealed that Ttyh1 binds to the regulator of γ-secretase activity Rer1 in the endoplasmic reticulum and thereby destabilizes Rer1 protein levels. This is the key step for Ttyh1-dependent enhancement of γ-secretase activity, as Rer1 overexpression completely abolishes the effects of Ttyh1 on NSC maintenance. Taken together, these findings indicate that Ttyh1 plays an important role during mammalian brain development by positively regulating the Notch signaling pathway through the downregulation of Rer1.

UI MeSH Term Description Entries
D008565 Membrane Proteins Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D051880 Receptors, Notch A family of conserved cell surface receptors that contain EPIDERMAL GROWTH FACTOR repeats in their extracellular domain and ANKYRIN REPEATS in their cytoplasmic domains. The cytoplasmic domains are released upon ligand binding and translocate to the CELL NUCLEUS, where they act as transcription factors. Notch Protein,Notch Receptor,Notch Receptors,Notch Proteins,Protein, Notch,Receptor, Notch
D053829 Amyloid Precursor Protein Secretases Endopeptidases that are specific for AMYLOID PROTEIN PRECURSOR. Three secretase subtypes referred to as alpha, beta, and gamma have been identified based upon the region of amyloid protein precursor they cleave. APP Secretase,Amyloid Precursor Protein Secretase,Secretase,Secretases,alpha-Secretase,beta-Secretase,gamma-Secretase,Secretase, APP,alpha Secretase,beta Secretase,gamma Secretase
D058953 Neural Stem Cells Self-renewing cells that generate the main phenotypes of the nervous system in both the embryo and adult. Neural stem cells are precursors to both NEURONS and NEUROGLIA. Cell, Neural Stem,Cells, Neural Stem,Neural Stem Cell,Stem Cell, Neural,Stem Cells, Neural

Related Publications

Juwan Kim, and Dasol Han, and Sung-Hyun Byun, and Mookwang Kwon, and Jae Youl Cho, and Samuel J Pleasure, and Keejung Yoon
May 2019, Biochemical and biophysical research communications,
Juwan Kim, and Dasol Han, and Sung-Hyun Byun, and Mookwang Kwon, and Jae Youl Cho, and Samuel J Pleasure, and Keejung Yoon
June 2010, Genes to cells : devoted to molecular & cellular mechanisms,
Juwan Kim, and Dasol Han, and Sung-Hyun Byun, and Mookwang Kwon, and Jae Youl Cho, and Samuel J Pleasure, and Keejung Yoon
March 2008, Stem cells (Dayton, Ohio),
Juwan Kim, and Dasol Han, and Sung-Hyun Byun, and Mookwang Kwon, and Jae Youl Cho, and Samuel J Pleasure, and Keejung Yoon
February 2023, EMBO reports,
Juwan Kim, and Dasol Han, and Sung-Hyun Byun, and Mookwang Kwon, and Jae Youl Cho, and Samuel J Pleasure, and Keejung Yoon
June 2019, Biochemical and biophysical research communications,
Juwan Kim, and Dasol Han, and Sung-Hyun Byun, and Mookwang Kwon, and Jae Youl Cho, and Samuel J Pleasure, and Keejung Yoon
August 2014, Biotechnology letters,
Juwan Kim, and Dasol Han, and Sung-Hyun Byun, and Mookwang Kwon, and Jae Youl Cho, and Samuel J Pleasure, and Keejung Yoon
February 2022, Development (Cambridge, England),
Juwan Kim, and Dasol Han, and Sung-Hyun Byun, and Mookwang Kwon, and Jae Youl Cho, and Samuel J Pleasure, and Keejung Yoon
July 2017, eLife,
Juwan Kim, and Dasol Han, and Sung-Hyun Byun, and Mookwang Kwon, and Jae Youl Cho, and Samuel J Pleasure, and Keejung Yoon
September 2019, Journal of molecular and cellular cardiology,
Juwan Kim, and Dasol Han, and Sung-Hyun Byun, and Mookwang Kwon, and Jae Youl Cho, and Samuel J Pleasure, and Keejung Yoon
January 2019, Frontiers in molecular neuroscience,
Copied contents to your clipboard!