Cortical anchoring of the microtubule cytoskeleton is essential for neuron polarity DOI Creative Commons
He Liu, Robbelien Kooistra, Ravi Das

et al.

eLife, Journal Year: 2020, Volume and Issue: 9

Published: April 15, 2020

The development of a polarized neuron relies on the selective transport proteins to axons and dendrites. Although it is well known that microtubule cytoskeleton has central role in establishing neuronal polarity, how its specific organization established maintained poorly understood. Using vivo model system Caenorhabditis elegans, we found highly conserved UNC-119 protein provides link between membrane-associated Ankyrin (UNC-44) microtubule-associated CRMP (UNC-33). Together they form periodic complex anchors axonal dendritic bundles cortex. This anchoring critical maintain by opposing kinesin-1 powered sliding. Disturbing this molecular alters polarity causes strong developmental defects nervous leading severely paralyzed animals.

Language: Английский

Cardiac microtubules in health and heart disease DOI Open Access
Matthew A. Caporizzo, Yingxian Chen, Benjamin L. Prosser

et al.

Experimental Biology and Medicine, Journal Year: 2019, Volume and Issue: 244(15), P. 1255 - 1272

Published: Aug. 9, 2019

Cardiomyocytes are large (∼40,000 µm 3 ), rod-shaped muscle cells that provide the working force behind each heartbeat. These highly structured packed with dense cytoskeletal networks can be divided into two groups—the contractile (i.e. sarcomeric) cytoskeleton consists of filamentous actin-myosin arrays organized myofibrils, and non-sarcomeric cytoskeleton, which is composed β- γ-actin, microtubules, intermediate filaments. Together, microtubules filaments form a cross-linked scaffold, these responsible for delivery intracellular cargo, transmission mechanical signals, shaping membrane systems, organization myofibrils organelles. Microtubules extensively altered as part both adaptive pathological cardiac remodeling, has diverse ramifications structure function cardiomyocyte. In heart failure, proliferation post-translational modification microtubule network linked to number maladaptive processes, including impediment cardiomyocyte contraction relaxation. This raises possibility reversing alterations could improve performance, yet therapeutic efforts will strongly benefit from deeper understanding basic biology in heart. The aim this review summarize known physiological roles network, consequences its highlight open intriguing questions regarding microtubules. Impact statement Advancements cell biological biophysical approaches super-resolution imaging have greatly broadened our view tubulin over last decade. heart, microtubule-based transport help organize maintain key structures within cardiomyocyte, sarcomere, intercalated disc, protein clearance machinery transverse-tubule sarcoplasmic reticulum membranes. It become increasingly clear post translational regulation determinant their sub-cellular functionality. Alterations density, stability, modifications hallmarks modified directly impede various forms disease. summarizes functional multi-leveled highlights how refined experimental techniques shedding mechanistic clarity on regionally specified physiology pathophysiology.

Language: Английский

Citations

94

MARK4 controls ischaemic heart failure through microtubule detyrosination DOI Open Access
Xianjun Yu, Chen Xiao, Mamta Amrute‐Nayak

et al.

Nature, Journal Year: 2021, Volume and Issue: 594(7864), P. 560 - 565

Published: May 26, 2021

Language: Английский

Citations

78

Microtubule-associated protein MAP7 promotes tubulin posttranslational modifications and cargo transport to enable osmotic adaptation DOI
Yusheng Shen, Kassandra M Ori-McKenney

Developmental Cell, Journal Year: 2024, Volume and Issue: 59(12), P. 1553 - 1570.e7

Published: April 3, 2024

Language: Английский

Citations

12

Doublecortin restricts neuronal branching by regulating tubulin polyglutamylation DOI Creative Commons
Muriel Sébastien, Alexandra Paquette, Emily N. P. Prowse

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 18, 2025

Doublecortin is a neuronal microtubule-associated protein that regulates microtubule structure in neurons. Mutations cause lissencephaly and subcortical band heterotopia by impairing migration. We use CRISPR/Cas9 to knock-out the gene induced pluripotent stem cells differentiate into cortical DCX-KO neurons show reduced velocities of nuclear movements an increased number neurites early development, consistent with previous findings. Neurite branching regulated host proteins, as well polymerization dynamics. However, EB comet dynamics are unchanged Rather, we observe significant reduction α-tubulin polyglutamylation Polyglutamylation levels rescued expression or TTLL11, glutamylase. Using U2OS orthogonal model system, DCX TTLL11 act synergistically promote polyglutamylation. propose acts positive regulator restricts neurite branching. Our results indicate unexpected role for homeostasis tubulin code. Lissencephaly severe neurodevelopmental disease often caused mutations Dcx gene. human cellular lissencephaly, authors report activating

Language: Английский

Citations

1

MAP7 regulates axon morphogenesis by recruiting kinesin-1 to microtubules and modulating organelle transport DOI Creative Commons
Stephen R. Tymanskyj, Benjamin H Yang, Kristen J. Verhey

et al.

eLife, Journal Year: 2018, Volume and Issue: 7

Published: Aug. 22, 2018

Neuronal cell morphogenesis depends on proper regulation of microtubule-based transport, but the underlying mechanisms are not well understood. Here, we report our study MAP7, a unique microtubule-associated protein that interacts with both microtubules and motor kinesin-1. Structure-function analysis in rat embryonic sensory neurons shows kinesin-1 interacting domain MAP7 is required for axon branch growth formation. Also, two microtubule binding sites found have distinct dissociation kinetics Furthermore, recruits dynamically to microtubules, leading alterations organelle transport behaviors, particularly pause/speed switching. As localized sites, results suggest novel mechanism mediated by dual interactions precise control during morphogenesis.

Language: Английский

Citations

71

Microtubules: Evolving roles and critical cellular interactions DOI Open Access
Caitlin M. Logan, A. Sue Menko

Experimental Biology and Medicine, Journal Year: 2019, Volume and Issue: 244(15), P. 1240 - 1254

Published: Aug. 6, 2019

Microtubules are cytoskeletal elements known as drivers of directed cell migration, vesicle and organelle trafficking, mitosis. In this review, we discuss new research in the lens that has shed light into further roles for stable microtubules process development morphogenesis. lens, well other systems, distinct characteristically dynamic stabilized populations coming to light. Understanding mechanisms microtubule stabilization associated post-translational modifications is an evolving field study. Appropriate cellular homeostasis relies on not only one element, but also rather interaction between proteins regulators. key integrators with actin intermediate filaments, cell–cell junctional regulators including myosin RhoGTPases maintain balance. Impact statement The role functioning constantly expanding. examine exciting fields discovery microtubule’s involvement morphogenesis, highlight our understanding differential versus subpopulations, a integrator.

Language: Английский

Citations

71

MAP7 regulates organelle transport by recruiting kinesin-1 to microtubules DOI Creative Commons
Abdullah R. Chaudhary, Hailong Lu,

Elena B. Krementsova

et al.

Journal of Biological Chemistry, Journal Year: 2019, Volume and Issue: 294(26), P. 10160 - 10171

Published: May 13, 2019

Language: Английский

Citations

70

Phosphatidylinositol 3-kinase signalling is spatially organized at endosomal compartments by microtubule-associated protein 4 DOI

Narendra Thapa,

Mo Chen, Hudson T. Horn

et al.

Nature Cell Biology, Journal Year: 2020, Volume and Issue: 22(11), P. 1357 - 1370

Published: Nov. 1, 2020

Language: Английский

Citations

66

Microtubule associated proteins as targets for anticancer drug development DOI

Sadiya Khwaja,

Kapil Kumar,

Ranjana Das

et al.

Bioorganic Chemistry, Journal Year: 2021, Volume and Issue: 116, P. 105320 - 105320

Published: Aug. 31, 2021

Language: Английский

Citations

47

Combinatorial and antagonistic effects of tubulin glutamylation and glycylation on katanin microtubule severing DOI Creative Commons
Ewa Szczęsna, Elena A. Zehr,

Steven W. Cummings

et al.

Developmental Cell, Journal Year: 2022, Volume and Issue: 57(21), P. 2497 - 2513.e6

Published: Nov. 1, 2022

Language: Английский

Citations

33