The Septate Junction Protein Tsp2A Restricts Intestinal Stem Cell Activity via Endocytic Regulation of aPKC and Hippo Signaling.

Cell Proliferation Humans Intestines / physiopathology Protein Kinase C / metabolism Signal Transduction Stem Cells / metabolism Tetraspanins / metabolism
Drosophila midgut Hippo signaling Tsp2A aPKC endocytosis intestinal stem cells septate junction

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
15 01 2019
Historique:
received: 06 02 2018
revised: 24 07 2018
accepted: 17 12 2018
entrez: 17 1 2019
pubmed: 17 1 2019
medline: 10 4 2020
Statut: ppublish

Résumé

Hippo signaling and the activity of its transcriptional coactivator, Yorkie (Yki), are conserved and crucial regulators of tissue homeostasis. In the Drosophila midgut, after tissue damage, Yki activity increases to stimulate stem cell proliferation, but how Yki activity is turned off once the tissue is repaired is unknown. From an RNAi screen, we identified the septate junction (SJ) protein tetraspanin 2A (Tsp2A) as a tumor suppressor. Tsp2A undergoes internalization to facilitate the endocytic degradation of atypical protein kinase C (aPKC), a negative regulator of Hippo signaling. In the Drosophila midgut epithelium, adherens junctions (AJs) and SJs are prominent in intestinal stem cells or enteroblasts (ISCs or EBs) and enterocytes (ECs), respectively. We show that when ISCs differentiate toward ECs, Tsp2A is produced, participates in SJ assembly, and turns off aPKC and Yki-JAK-Stat activity. Altogether, our study uncovers a mechanism allowing the midgut to restore Hippo signaling and restrict proliferation once tissue repair is accomplished.

Identifiants

DOI: 10.1016/j.celrep.2018.12.079 PMID: 30650359 PMC: PMC6394833
pubmed: 30650359
pii: S2211-1247(18)32024-2
doi: 10.1016/j.celrep.2018.12.079
pmc: PMC6394833
mid: NIHMS1011709
pii:
doi:

Substances chimiques

TSPAN32 protein, human 0
Tetraspanins 0
PKC-3 protein EC 2.7.11.13
Protein Kinase C EC 2.7.11.13

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

670-688.e6

Subventions

Organisme : NIGMS NIH HHS
ID : R01 GM067761
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States

Informations de copyright

Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

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Auteurs

Chiwei Xu (C)

Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.

Hong-Wen Tang (HW)

Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.

Ruei-Jiun Hung (RJ)

Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.

Yanhui Hu (Y)

Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.

Xiaochun Ni (X)

Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.

Benjamin E Housden (BE)

Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.

Norbert Perrimon (N)

Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. Electronic address: perrimon@receptor.med.harvard.edu.

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Classifications MeSH

questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › The Septate Junction Protein Tsp2A Restricts...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › The Septate Junction Protein Tsp2A Restricts...
questionsmedicales.fr › Système digestif › Tube digestif › Intestins › The Septate Junction Protein Tsp2A Restricts...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Protéine kinase C › The Septate Junction Protein Tsp2A Restricts...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › The Septate Junction Protein Tsp2A Restricts...
questionsmedicales.fr › Cellules › Cellules souches › The Septate Junction Protein Tsp2A Restricts...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Tétraspanines › The Septate Junction Protein Tsp2A Restricts...