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Before cell division, mitotic spindle is assembled from chromosomes and centrosomes. After the cell division, Golgi organelles assemble from multiple vesicles scattered across daughter cells. These are among many other examples of intracellular assembly of vesicles, organelles and chromosomes made possible by dynamic microtubules. The most prominent microtubule networks are centrosome-focused asters that 'search' for the vesicles and chromosomes, but there are also microtubules originating from the vesicles and chromosomes, raising the question whether a coordination between multiple microtubule networks optimizes the assembly process. This study uses a computational model to examine how microtubule dynamics influence the assembly of organelles from vesicles. The model includes two microtubule populations: microtubules anchored to the vesicles, which drive local clustering, and 'central' microtubules anchored to the centrosome that aggregate the vesicles globally. Simulations show that a microtubule decentralization - balanced contribution from both microtubule populations - accelerates the assembly of tens of vesicles, but that assigning all microtubules to hundreds of vesicles optimizes the assembly. Directionally biased microtubule growth, particularly when avoiding spontaneous catastrophe events, further accelerates the assembly. Additionally, microtubule branching, when occurring at optimal angles and spacings, enhances the assembly's efficiency. Lastly, rapid crosslinking of overlapping central and 'local' microtubules can drastically accelerate the assembly. Applying this model to the spindle assembly in early mitosis reveals similar insights. The model suggests that the observed multiple microtubule networks optimize the intracellular assembly processes when molecular resources are limited.
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http://dx.doi.org/10.1016/j.bpj.2025.08.016 | DOI Listing |
Mol Biol Cell
September 2025
Department of Cell and Developmental Biology, Vanderbilt University School of Medicine Basic Sciences, Nashville, TN, USA.
Cardiac sarcomere assembly is a highly orchestrated process requiring integration between intracellular contractile machinery and extracellular adhesions. While α-actinin-2 (ACTN2) is well known for its structural role at the cardiac Z-disc, the sarcomere border, the function of the "non-muscle" paralog α-actinin-1 (ACTN1) in cardiac myocytes remains unclear. Using human induced pluripotent stem cell-derived cardiac myocytes (hiCMs), we demonstrate that siRNA-mediated depletion of ACTN1 disrupts sarcomere assembly, and that exogenous re-introduction of ACTN1 but not ACTN2 restores assembly, revealing non-redundant functions.
View Article and Find Full Text PDFMater Today Bio
October 2025
School of Pharmacy, Henan Medical University, Xinxiang, Henan, China.
Breast cancer continues to present a major clinical hurdle, largely attributable to its aggressive metastatic behavior and the suboptimal efficacy of standard chemotherapeutic regimens. Cisplatin (CDDP) is a representative platinum drug in the treatment of breast cancer, however, its therapeutic application is often constrained by systemic toxicity and the frequent onset of chemoresistance. Here, we introduce a novel charge-adaptive nanoprodrug system, referred to as PP@, engineered to respond to tumor-specific conditions.
View Article and Find Full Text PDFNat Rev Mol Cell Biol
September 2025
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA.
The defining property of eukaryotic cells is the storage of heritable genetic material in a nuclear compartment. For eukaryotic cells to carry out the myriad biochemical processes necessary for their function, macromolecules must be efficiently exchanged between the nucleus and cytoplasm. The nuclear pore complex (NPC) - which is a massive assembly of ~35 different proteins present in multiple copies totalling ~1,000 protein subunits and architecturally conserved across eukaryotes - establishes a size-selective channel for regulated bidirectional transport of folded macromolecules and macromolecular assemblies across the nuclear envelope.
View Article and Find Full Text PDFJ Cell Biol
October 2025
Autophagy, Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
The mechanisms governing mammalian proton pump V-ATPase function are of fundamental and medical interest. The assembly and disassembly of cytoplasmic V1 domain with the membrane-embedded V0 domain of V-ATPase is a key aspect of V-ATPase localization and function. Here, we show that the mammalian protein ATG16L1, primarily appreciated for its role in canonical autophagy and in noncanonical membrane atg8ylation processes, controls V-ATPase.
View Article and Find Full Text PDFVet Microbiol
September 2025
University of Kentucky Veterinary Diagnostic Laboratory, Lexington, KY 40511, United States of America. Electronic address:
Neorickettsia risticii (N. risticii) is an obligatory intracellular bacterium that causes Potomac horse fever (PHF), a disease clinically characterized by diarrhea, pyrexia, and laminitis in horses. Although sporadic reports of N.
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