Microtubule minus-end regulation at spindle poles by an ASPM-katanin complex. 2017

Kai Jiang, and Lenka Rezabkova, and Shasha Hua, and Qingyang Liu, and Guido Capitani, and A F Maarten Altelaar, and Albert J R Heck, and Richard A Kammerer, and Michel O Steinmetz, and Anna Akhmanova
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.

ASPM (known as Asp in fly and ASPM-1 in worm) is a microcephaly-associated protein family that regulates spindle architecture, but the underlying mechanism is poorly understood. Here, we show that ASPM forms a complex with another protein linked to microcephaly, the microtubule-severing ATPase katanin. ASPM and katanin localize to spindle poles in a mutually dependent manner and regulate spindle flux. X-ray crystallography revealed that the heterodimer formed by the N- and C-terminal domains of the katanin subunits p60 and p80, respectively, binds conserved motifs in ASPM. Reconstitution experiments demonstrated that ASPM autonomously tracks growing microtubule minus ends and inhibits their growth, while katanin decorates and bends both ends of dynamic microtubules and potentiates the minus-end blocking activity of ASPM. ASPM also binds along microtubules, recruits katanin and promotes katanin-mediated severing of dynamic microtubules. We propose that the ASPM-katanin complex controls microtubule disassembly at spindle poles and that misregulation of this process can lead to microcephaly.

UI MeSH Term Description Entries
D008831 Microcephaly A congenital abnormality in which the CEREBRUM is underdeveloped, the fontanels close prematurely, and, as a result, the head is small. (Desk Reference for Neuroscience, 2nd ed.) Microlissencephaly,Severe Congenital Microcephaly,Congenital Microcephalies, Severe,Congenital Microcephaly, Severe,Microcephalies,Microcephalies, Severe Congenital,Microcephaly, Severe Congenital,Microlissencephalies,Severe Congenital Microcephalies
D008870 Microtubules Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein TUBULIN and are influenced by TUBULIN MODULATORS. Microtubule
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D009419 Nerve Tissue Proteins Proteins, Nerve Tissue,Tissue Proteins, Nerve
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D011487 Protein Conformation The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). Conformation, Protein,Conformations, Protein,Protein Conformations
D006367 HeLa Cells The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for, among other things, VIRUS CULTIVATION and PRECLINICAL DRUG EVALUATION assays. Cell, HeLa,Cells, HeLa,HeLa Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000074201 Katanin An enzyme (AAA ATPase) consisting of the 60 kDa ATPase subunit (p60 subunit A1) which severs MICROTUBULES, and an 80 kDa accessory protein (p80 subunit B1), which targets the enzyme to the CENTROSOME. It releases microtubules from the mitotic SPINDLE POLES to allow depolymerization and poleward motion of chromosomes. It is also a regulator of microtubule dynamics in NEURONAL OUTGROWTH.

Related Publications

Kai Jiang, and Lenka Rezabkova, and Shasha Hua, and Qingyang Liu, and Guido Capitani, and A F Maarten Altelaar, and Albert J R Heck, and Richard A Kammerer, and Michel O Steinmetz, and Anna Akhmanova
March 2018, Structure (London, England : 1993),
Kai Jiang, and Lenka Rezabkova, and Shasha Hua, and Qingyang Liu, and Guido Capitani, and A F Maarten Altelaar, and Albert J R Heck, and Richard A Kammerer, and Michel O Steinmetz, and Anna Akhmanova
June 2019, Journal of cell science,
Kai Jiang, and Lenka Rezabkova, and Shasha Hua, and Qingyang Liu, and Guido Capitani, and A F Maarten Altelaar, and Albert J R Heck, and Richard A Kammerer, and Michel O Steinmetz, and Anna Akhmanova
October 2005, The Journal of cell biology,
Kai Jiang, and Lenka Rezabkova, and Shasha Hua, and Qingyang Liu, and Guido Capitani, and A F Maarten Altelaar, and Albert J R Heck, and Richard A Kammerer, and Michel O Steinmetz, and Anna Akhmanova
August 2021, The Journal of cell biology,
Kai Jiang, and Lenka Rezabkova, and Shasha Hua, and Qingyang Liu, and Guido Capitani, and A F Maarten Altelaar, and Albert J R Heck, and Richard A Kammerer, and Michel O Steinmetz, and Anna Akhmanova
July 2015, Current biology : CB,
Kai Jiang, and Lenka Rezabkova, and Shasha Hua, and Qingyang Liu, and Guido Capitani, and A F Maarten Altelaar, and Albert J R Heck, and Richard A Kammerer, and Michel O Steinmetz, and Anna Akhmanova
April 2014, Proceedings of the National Academy of Sciences of the United States of America,
Kai Jiang, and Lenka Rezabkova, and Shasha Hua, and Qingyang Liu, and Guido Capitani, and A F Maarten Altelaar, and Albert J R Heck, and Richard A Kammerer, and Michel O Steinmetz, and Anna Akhmanova
January 2014, The EMBO journal,
Kai Jiang, and Lenka Rezabkova, and Shasha Hua, and Qingyang Liu, and Guido Capitani, and A F Maarten Altelaar, and Albert J R Heck, and Richard A Kammerer, and Michel O Steinmetz, and Anna Akhmanova
February 2001, The Journal of cell biology,
Kai Jiang, and Lenka Rezabkova, and Shasha Hua, and Qingyang Liu, and Guido Capitani, and A F Maarten Altelaar, and Albert J R Heck, and Richard A Kammerer, and Michel O Steinmetz, and Anna Akhmanova
April 1991, European journal of cell biology,
Kai Jiang, and Lenka Rezabkova, and Shasha Hua, and Qingyang Liu, and Guido Capitani, and A F Maarten Altelaar, and Albert J R Heck, and Richard A Kammerer, and Michel O Steinmetz, and Anna Akhmanova
May 2000, Journal of cell science,
Copied contents to your clipboard!