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DIDO3 Regulates Microtubule Stability at Transcriptional and Posttranslational Levels and is Needed for Fibroblast Adhesion and Movement

75 Pages Posted: 30 Jul 2019 Sneak Peek Status: Review Complete

See all articles by Cristina Pacios-Bras

Cristina Pacios-Bras

Spanish National Research Council - Immunology and Oncology Department

Tirso Pons

Spanish National Research Council - Immunology and Oncology Department

Astrid Alonso-Guerrero

Spanish National Research Council - Immunology and Oncology Department

Sara Román-García

Spanish National Research Council - Immunology and Oncology Department

Julio Gutiérrez

Spanish National Research Council - Immunology and Oncology Department

Pablo Manrique

Spanish National Research Council - Immunology and Oncology Department

Fernando Gutiérrez del Burgo

Spanish National Research Council - Immunology and Oncology Department

Ricardo Villares

Spanish National Research Council - Immunology and Oncology Department

Carmen Mora Gallardo

Spanish National Research Council - Immunology and Oncology Department

Karel H.M. van Wely

Spanish National Research Council - Immunology and Oncology Department

Yolanda R. Carrasco

Spanish National Research Council - Immunology and Oncology Department

Carlos Martínez-A

Spanish National Research Council - Immunology and Oncology Department

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Abstract

Microtubule (MT) dynamics are central to eukaryotic cell organization, intracellular transport, division, adhesion, polarization, and migration. Unbalanced MT stability is associated with metastasis and neurodegenerative diseases. We show that altered expression of death-inducer obliterator isoform 3 (DIDO3) restricts cell adhesion and motility. Fibroblasts with a DIDO3 C-terminal delection (DIDO3ΔCT) show i) MT bundling and looping, ii) failure to localize the tubulin plus-end binding protein CLASP2 to the membrane, iii) deregulated tubulin-actin-binding proteins EB1, GAS2L1, and DNM1 downstream of GSK3β, and iv) transcriptionally deregulated cytoskeletal- and non-cytoskeletal-coding genes (Gas2l1, Dnm1, Tubb4a, Obsl1 and Sema7a, Lgals3bp, Cct3, respectively) associated to cell migration, adhesion, immune responses, and tubulin-actin folding. DIDO3ΔCT deletion delocalizes the GSK3β-interacting protein ninein and prevents MT growth from the centrosome. DIDO3 expression in DIDO3ΔCT fibroblasts largely reestablishes the normal phenotype. Furthermore, DIDO3ΔCT B cells do not polarize the centrosome to the immunological synapse, a tubulin-dependent process. DIDO3CT overexpression induces tubulin stabilization and CLASP2 accumulation at the cell membrane. We propose a mechanism by which DIDO3 links transcriptional and posttranslational regulation of MT stability.

Suggested Citation

Pacios-Bras, Cristina and Pons, Tirso and Alonso-Guerrero, Astrid and Román-García, Sara and Gutiérrez, Julio and Manrique, Pablo and Gutiérrez del Burgo, Fernando and Villares, Ricardo and Mora Gallardo, Carmen and H.M. van Wely, Karel and Carrasco, Yolanda R. and Martínez-A, Carlos, DIDO3 Regulates Microtubule Stability at Transcriptional and Posttranslational Levels and is Needed for Fibroblast Adhesion and Movement (July 27, 2019). Available at SSRN: https://ssrn.com/abstract=3428482 or http://dx.doi.org/10.2139/ssrn.3428482
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Cristina Pacios-Bras (Contact Author)

Spanish National Research Council - Immunology and Oncology Department ( email )

Darwin 3
Madrid, 28049
Spain

Tirso Pons

Spanish National Research Council - Immunology and Oncology Department

Darwin 3
Madrid, 28049
Spain

Astrid Alonso-Guerrero

Spanish National Research Council - Immunology and Oncology Department

Darwin 3
Madrid, 28049
Spain

Sara Román-García

Spanish National Research Council - Immunology and Oncology Department

Darwin 3
Madrid, 28049
Spain

Julio Gutiérrez

Spanish National Research Council - Immunology and Oncology Department

Darwin 3
Madrid, 28049
Spain

Pablo Manrique

Spanish National Research Council - Immunology and Oncology Department

Darwin 3
Madrid, 28049
Spain

Fernando Gutiérrez del Burgo

Spanish National Research Council - Immunology and Oncology Department

Darwin 3
Madrid, 28049
Spain

Ricardo Villares

Spanish National Research Council - Immunology and Oncology Department

Darwin 3
Madrid, 28049
Spain

Carmen Mora Gallardo

Spanish National Research Council - Immunology and Oncology Department

Darwin 3
Madrid, 28049
Spain

Karel H.M. van Wely

Spanish National Research Council - Immunology and Oncology Department

Darwin 3
Madrid, 28049
Spain

Yolanda R. Carrasco

Spanish National Research Council - Immunology and Oncology Department

Darwin 3
Madrid, 28049
Spain

Carlos Martínez-A

Spanish National Research Council - Immunology and Oncology Department

Darwin 3
Madrid, 28049
Spain

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