scholarly journals The mitotic kinesin-14 KlpA contains a context-dependent directionality switch

2016 ◽  
Author(s):  
Andrew R. Popchock ◽  
Kuo-Fu Tseng ◽  
Pan Wang ◽  
P. Andrew Karplus ◽  
Xin Xiang ◽  
...  
Keyword(s):  
Aspergillus Nidulans ◽  
Filamentous Fungus ◽  
Mitotic Spindle ◽  
Atp Hydrolysis ◽  
Binding Domain ◽  
Microtubule Binding ◽  
Microtubule Binding Domain ◽  
Directed Motility ◽  
Mitotic Spindle Assembly ◽  
Context Dependent

AbstractKinesins are microtubule-based motor proteins that convert chemical energy from ATP hydrolysis into mechanical work for a variety of essential intracellular processes. Kinesin-14s (i.e. kinesins with a C-terminal motor domain) are commonly considered to be nonprocessive minus end-directed motors that mainly function for mitotic spindle assembly and maintenance. Here, we show that KlpA – a mitotic kinesin-14 motor from the filamentous fungus Aspergillus nidulans – contains a context-dependent directionality switch. KlpA exhibits canonical minus end-directed motility inside microtubule bundles, but on individual microtubules it unexpectedly moves processively toward the plus ends. Removal of the N-terminal nonmotor microtubule-binding domain renders KlpA diffusive on individual microtubules but does not abolish its minus end-directed motility to collectively glide microtubules, suggesting that the nonmotor microtubule-binding domain likely acts as a switch for controlling the direction of KlpA motility. Collectively, these findings provide important insights into the mechanism and regulation of KlpA functions inside the mitotic spindle.

scholarly journals HookA is a novel dynein–early endosome linker critical for cargo movement in vivo

2014 ◽  
Vol 204 (6) ◽  
pp. 1009-1026 ◽  
Author(s):  
Jun Zhang ◽  
Rongde Qiu ◽  
Herbert N. Arst ◽  
Miguel A. Peñalva ◽  
Xin Xiang
Keyword(s):  
Aspergillus Nidulans ◽  
Filamentous Fungus ◽  
Coiled Coil ◽  
Cytoplasmic Dynein ◽  
Early Endosome ◽  
Genetic Screen ◽  
Binding Domain ◽  
Terminal Part ◽  
Microtubule Binding Domain

Cytoplasmic dynein transports membranous cargoes along microtubules, but the mechanism of dynein–cargo interaction is unclear. From a genetic screen, we identified a homologue of human Hook proteins, HookA, as a factor required for dynein-mediated early endosome movement in the filamentous fungus Aspergillus nidulans. HookA contains a putative N-terminal microtubule-binding domain followed by coiled-coil domains and a C-terminal cargo-binding domain, an organization reminiscent of cytoplasmic linker proteins. HookA–early endosome interaction occurs independently of dynein–early endosome interaction and requires the C-terminal domain. Importantly, HookA interacts with dynein and dynactin independently of HookA–early endosome interaction but dependent on the N-terminal part of HookA. Both dynein and the p25 subunit of dynactin are required for the interaction between HookA and dynein–dynactin, and loss of HookA significantly weakens dynein–early endosome interaction, causing a virtually complete absence of early endosome movement. Thus, HookA is a novel linker important for dynein–early endosome interaction in vivo.

scholarly journals Structure and Functional Role of Dynein's Microtubule-Binding Domain

Science ◽  
2008 ◽  
Vol 322 (5908) ◽  
pp. 1691-1695 ◽  
Author(s):  
A. P. Carter ◽  
J. E. Garbarino ◽  
E. M. Wilson-Kubalek ◽  
W. E. Shipley ◽  
C. Cho ◽  
...  
Keyword(s):  
Functional Role ◽  
Binding Domain ◽  
Microtubule Binding ◽  
Microtubule Binding Domain

scholarly journals Autoregulatory control of microtubule binding in doublecortin-like kinase 1

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Regina L Agulto ◽  
Melissa M Rogers ◽  
Tracy C Tan ◽  
Amrita Ramkumar ◽  
Ashlyn M Downing ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Therapeutic Target ◽  
Kinase Activity ◽  
Kinase Inhibitors ◽  
Binding Domain ◽  
Cancer Development ◽  
Microtubule Binding ◽  
Microtubule Binding Domain

The microtubule-associated protein, doublecortin-like kinase 1 (DCLK1), is highly expressed in a range of cancers and is a prominent therapeutic target for kinase inhibitors. The physiological roles of DCLK1 kinase activity and how it is regulated remain elusive. Here, we analyze the role of mammalian DCLK1 kinase activity in regulating microtubule binding. We find that DCLK1 autophosphorylates a residue within its C-terminal tail to restrict its kinase activity and prevent aberrant hyperphosphorylation within its microtubule-binding domain. Removal of the C-terminal tail or mutation of this residue causes an increase in phosphorylation within the doublecortin domains, which abolishes microtubule binding. Therefore, autophosphorylation at specific sites within DCLK1 have diametric effects on the molecule's association with microtubules. Our results suggest a mechanism by which DCLK1 modulates its kinase activity to tune its microtubule-binding affinity. These results provide molecular insights for future therapeutic efforts related to DCLK1's role in cancer development and progression.

The projection domain of MAP2b regulates microtubule protrusion and process formation in Sf9 cells

2002 ◽  
Vol 115 (7) ◽  
pp. 1523-1539 ◽  
Author(s):  
Dave Bélanger ◽  
Carole Abi Farah ◽  
Minh Dang Nguyen ◽  
Michel Lauzon ◽  
Sylvie Cornibert ◽  
...  
Keyword(s):  
Cell Surface ◽  
Binding Domain ◽  
Intramolecular Interactions ◽  
Microtubule Assembly ◽  
Sf9 Cells ◽  
Microtubule Binding ◽  
Process Formation ◽  
Microtubule Binding Domain ◽  
Projection Domain

The expression of microtubule-associated protein 2 (MAP2), developmentally regulated by alternative splicing, coincides with neurite outgrowth. MAP2 proteins contain a microtubule-binding domain (C-terminal) that promotes microtubule assembly and a poorly characterized domain, the projection domain(N-terminal), extending at the surface of microtubules. MAP2b differs from MAP2c by an additional sequence of 1372 amino acids in the projection domain. In this study, we examined the role of the projection domain in the protrusion of microtubules from the cell surface and the subsequent process formation in Sf9 cells. In this system, MAP2b has a lower capacity to induce process formation than MAP2c. To investigate the role of the projection domain in this event, we expressed truncated forms of MAP2b and MAP2c that have partial or complete deletion of their projection domain in Sf9 cells. Our results indicate that process formation is induced by the microtubule-binding domain of these MAP2 proteins and is regulated by their projection domain. Furthermore, the microtubule-binding activity of MAP2b and MAP2c truncated forms as well as the structural properties of the microtubule bundles induced by them do not seem to be the only determinants that control the protrusion of microtubules from the cell surface in Sf9 cells. Rather, our data suggest that microtubule protrusion and process formation are regulated by intramolecular interactions between the projection domain and its microtubule-binding domain in MAP2b.

Conformational transition state is responsible for assembly of microtubule-binding domain of tau protein

2004 ◽  
Vol 315 (3) ◽  
pp. 659-663 ◽  
Author(s):  
Shuko Hiraoka ◽  
Tian-Ming Yao ◽  
Katsuhiko Minoura ◽  
Koji Tomoo ◽  
Miho Sumida ◽  
...  
Keyword(s):  
Transition State ◽  
Tau Protein ◽  
Conformational Transition ◽  
Binding Domain ◽  
Microtubule Binding ◽  
Microtubule Binding Domain

Phosphorylation regulates fibrillation of an aggregation core peptide in the second repeat of microtubule-binding domain of human tau

2014 ◽  
Vol 22 (22) ◽  
pp. 6471-6480 ◽  
Author(s):  
Masafumi Inoue ◽  
Shinji Kaida ◽  
Shun Nakano ◽  
Chiara Annoni ◽  
Eiji Nakata ◽  
...  
Keyword(s):  
Binding Domain ◽  
Microtubule Binding ◽  
Microtubule Binding Domain ◽  
Core Peptide

scholarly journals Backbone and partial side chain assignment of the microtubule binding domain of the MAP1B light chain

2013 ◽  
Vol 8 (1) ◽  
pp. 123-127 ◽  
Author(s):  
Zsuzsanna Orbán-Németh ◽  
Morkos A. Henen ◽  
Leonhard Geist ◽  
Szymon Żerko ◽  
Saurabh Saxena ◽  
...  
Keyword(s):  
Light Chain ◽  
Binding Domain ◽  
Side Chain ◽  
Microtubule Binding ◽  
Microtubule Binding Domain
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