Intracellular trafficking events powered by microtubule-based molecular motors facilitate the targeted delivery of selected molecular components to specific neuronal subdomains. Within this context, we provide a brief review of mechanisms underlying the execution of axonal transport (AT) by conventional kinesin, the most abundant kinesin-related motor protein in the mature nervous system. We emphasize the biochemical heterogeneity of this multi-subunit motor protein, further discussing its significance in light of recent discoveries revealing its regulation by various protein kinases. In addition, we raise issues relevant to the mode of conventional kinesin attachment to cargoes and examine recent evidence linking alterations in conventional kinesin phosphorylation to the pathogenesis of adult-onset neurodegenerative diseases.
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http://dx.doi.org/10.1016/j.brainresbull.2016.06.009 | DOI Listing |
Biochem Pharmacol
December 2024
Center for Drug Discovery, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. Electronic address:
The discovery of new small-molecule inhibitors is essential to enhancing our understanding of biological events at the molecular level and driving advancements in drug discovery. Mitotic inhibitors have played a crucial role in development of anticancer drugs. Beyond traditional microtubule inhibitors, various inhibitors targeting specific mitotic factors have been developed.
View Article and Find Full Text PDFSoft Matter
December 2024
Departament de Ciència de Materials i Química Física, Universitat de Barcelona, Barcelona, Spain.
Sci Adv
August 2024
Weill Institute for Cell and Molecular Biology, Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
During animal development, the spatiotemporal properties of molecular events largely determine the biological outcomes. Conventional gene analysis methods lack the spatiotemporal resolution for precise dissection of developmental mechanisms. Although optogenetic tools exist for manipulating designer proteins in cultured cells, few have been successfully applied to endogenous proteins in live animals.
View Article and Find Full Text PDFKorean J Physiol Pharmacol
September 2024
Secretory proteins, including plasma membrane proteins, are generally known to be transported to the plasma membrane through the endoplasmic reticulum- to-Golgi pathway. However, recent studies have revealed that several plasma membrane proteins and cytosolic proteins lacking a signal peptide are released via an unconventional protein secretion (UcPS) route, bypassing the Golgi during their journey to the cell surface. For instance, transmembrane proteins such as the misfolded cystic fibrosis transmembrane conductance regulator (CFTR) protein and the Spike protein of coronaviruses have been observed to reach the cell surface through a UcPS pathway under cell stress conditions.
View Article and Find Full Text PDFNat Cell Biol
July 2024
State Key Laboratory of Membrane Biology, School of Pharmaceutical Sciences, Tsinghua University, Beijing, China.
Cargo translocation across membranes is a crucial aspect of secretion. In conventional secretion signal peptide-equipped proteins enter the endoplasmic reticulum (ER), whereas a subset of cargo lacking signal peptides translocate into the ER-Golgi intermediate compartment (ERGIC) in a process called unconventional protein secretion (UcPS). The regulatory events at the ERGIC in UcPS are unclear.
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