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

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159925PMC
http://dx.doi.org/10.7554/eLife.55111DOI Listing

Publication Analysis

Top Keywords

microtubule cytoskeleton
8
neuronal polarity
8
microtubule
5
cortical anchoring
4
anchoring microtubule
4
cytoskeleton essential
4
essential neuron
4
neuron polarity
4
polarity development
4
development polarized
4

Similar Publications

TCTEX1D2 is essential for sperm flagellum formation in mice.

Sci Rep

January 2025

Laboratory of Animal Reproduction and Development, Graduate School of Agricultural Science, Tohoku University, 468-1 Aramaki-Aoba, Aoba-Ku, Sendai, Miyagi, 980-8572, Japan.

Flagella and cilia are widely conserved motile structures, in mammalian, sperm possess flagella. Large protein complexes called dynein, including cytoplasmic dynein 2 and axonemal dynein, play a role in the formation of cilia and flagella. The function of each subunit component of dynein complexes in sperm flagellum formation remains unclear.

View Article and Find Full Text PDF

Data-Driven Equation-Free Dynamics Applied to Many-Protein Complexes: The Microtubule Tip Relaxation.

Biophys J

January 2025

Department of Chemistry, Chicago Center for Theoretical Chemistry, The James Franck Institute, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois 60637, United States. Electronic address:

Microtubules (MTs) constitute the largest components of the eukaryotic cytoskeleton and play crucial roles in various cellular processes, including mitosis and intracellular transport. The property allowing MTs to cater to such diverse roles is attributed to dynamic instability, which is coupled to the hydrolysis of GTP (guanosine-5'-triphosphate) to GDP (guanosine-5'-diphosphate) within the β-tubulin monomers. Understanding the equilibrium dynamics and the structural features of both GDP- and GTP-complexed MT tips, especially at an all-atom level, remains challenging for both experimental and computational methods because of their dynamic nature and the prohibitive computational demands of simulating large, many-protein systems.

View Article and Find Full Text PDF

NME7 maintains primary cilium assembly, ciliary microtubule stability, and Hedgehog signaling.

Life Sci Alliance

April 2025

https://ror.org/0040axw97 Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Center for Life Sciences, School of Life Sciences, Yunnan University, Kunming, China

NME7 (nucleoside diphosphate kinase 7), a lesser studied member of the non-metastatic expressed (NME) family, has been reported as a potential subunit of the γ-tubulin ring complex (γTuRC). However, its role in the cilium assembly and function remains unclear. Our research demonstrated that NME7 is located at the centrosome, including at the spindle poles during metaphase and at the basal bodies during cilium assembly.

View Article and Find Full Text PDF

Background: Pancreatic ductal adenocarcinoma (PDAC) is mostly refractory to immunotherapy due to immunosuppression in the tumor microenvironment and cancer cell-intrinsic T cell tolerance mechanisms. PDAC is described as a "cold" tumor type with poor infiltration by T cells and factors leading to intratumoral T cell suppression have thus received less attention. Here, we identify a cancer cell-intrinsic mechanism that contributes to a T cell-resistant phenotype and describes potential combinatorial therapy.

View Article and Find Full Text PDF

Diverse microtubule-binding repeats regulate TPX2 activities at distinct locations within the spindle.

J Cell Biol

March 2025

State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Medical Research Institute, Wuhan University, Wuhan, China.

TPX2 is an elongated molecule containing multiple α-helical repeats. It stabilizes microtubules (MTs), promotes MT nucleation, and is essential for spindle assembly. However, the molecular basis of how TPX2 performs these functions remains elusive.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!