Nuclear migration of newly born neurons is essential for cortex formation in the brain. The nucleus is translocated by actin and microtubules, yet the actual force generated by the interplay of these cytoskeletons remains elusive. High-resolution time-lapse observation of migrating murine cerebellar granule cells revealed that the nucleus actively rotates along the direction of its translocation, independently of centrosome motion. Pharmacological and molecular perturbation indicated that spin torque is primarily generated by microtubule motors through the LINC complex in the absence of actomyosin contractility. In contrast to the prevailing view that microtubules are uniformly oriented around the nucleus, we observed that the perinuclear microtubule arrays are of mixed polarity and both cytoplasmic dynein complex and kinesin-1 are required for nuclear rotation. Kinesin-1 can exert a point force on the nuclear envelope via association with nesprins, and loss of kinesin-1 causes failure in neuronal migration Thus, microtubules steer the nucleus and drive its rotation and translocation via a dynamic, focal interaction of nesprins with kinesin-1 and dynein, and this is necessary for neuronal migration during brain development.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1242/dev.158782 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Targeting STMN2 for neuroprotection and neuromuscular recovery in Spinal Muscular Atrophy: evidence from in vitro and in vivo SMA models.
Cell Mol Life Sci
December 2024
Department of Pathophysiology and Transplantation, Dino Ferrari Center, University of Milan, Milan, Italy.
The development of ground-breaking Survival Motor Neuron (SMN) replacement strategies has revolutionized the field of Spinal Muscular Atrophy (SMA) research. However, the limitations of these therapies have now become evident, highlighting the need for the development of complementary targets beyond SMN replacement. To address these challenges, here we explored, in in vitro and in vivo disease models, Stathmin-2 (STMN2), a neuronal microtubule regulator implicated in neurodegenerative diseases like Amyotrophic Lateral Sclerosis (ALS), as a novel SMN-independent target for SMA therapy.
View Article and Find Full Text PDFZYG-12/Hook's dual role as a dynein adaptor for early endosomes and nuclei is regulated by alternative splicing of its cargo binding domain.
Mol Biol Cell
December 2024
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.
The microtubule motor cytoplasmic dynein-1 transports and positions various organelles, but the molecular basis of this functional diversity is not fully understood. Cargo adaptors of the Hook protein family recruit dynein to early endosomes (EE) in fungi and human cells by forming the FTS-Hook-FHIP (FHF) complex. By contrast, the Hook homolog ZYG-12 recruits dynein to the nuclear envelope (NE) in the meiotic gonad and mitotic early embryo by forming a Linker of Nucleoskeleton and Cytoskeleton (LINC) complex.
View Article and Find Full Text PDFNonequilibrium Self-Assembly of Microtubules Through Stepwise Sequential Interactions of DNA.
Small
December 2024
Department of Physics, Kyoto University, Kyoto, 606-8224, Japan.
The assembly of biological systems forms nonequilibrium patterns with different functionalities through molecular-level communication via stepwise sequential interaction and activation. The mimicking of this molecular signaling offers extensive opportunities to design self-assemblies of bioinspired synthetic nonequilibrium systems to develop molecular robots with active, adaptive, and autonomous behavior. Herein, the design and construction of biomolecular motor system, microtubule (MT)-kinesin based molecular swarm system, are reported through stepwise sequential interactions of DNA.
View Article and Find Full Text PDFMETTL3-mediated CEP170 m6A modifications in spindle orientation and esophageal cancer cell proliferation.
Int Immunopharmacol
December 2024
Translational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China. Electronic address:
Esophageal cancer is a major malignancy with a high incidence and poor prognosis. To elucidate the mechanisms underlying its progression, particularly with respect to cell division and spindle orientation, we investigated the role of m6A modifications and the centrosomal protein CEP170. Using m6A-seq and RNA-seq of esophageal cancer tissues and adjacent normal tissues, we identified significant alterations in m6A modifications and gene expression, highlighting the upregulation and m6A enrichment of CEP170 in tumor tissues.
View Article and Find Full Text PDF[Cytoplasmic mRNA Transport: Adaptors of mRNA Binding to Microtubule Motor Proteins].
Mol Biol (Mosk)
December 2024
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.
The process of mRNA localization in the cytoplasm involves the directed transport of mRNP particles using the microtubule system. This transport is mediated and regulated by specific factors-adaptors between mRNA molecules and microtubule motor proteins. Adaptors are a key link in the mechanism of mRNA transport, but to date their identity and functioning are mostly unknown.
View Article and Find Full Text PDFWant 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!