Possible Role of Each Repeat Structure of the Microtubule-Binding Domain of the Tau Protein in In Vitro Aggregation

2005 ◽  
Vol 138 (4) ◽  
pp. 413-423 ◽  
Author(s):  
Koji Tomoo ◽  
Tian-Ming Yao ◽  
Katsuhiko Minoura ◽  
Shuko Hiraoka ◽  
Miho Sumida ◽  
...  
Keyword(s):  
Tau Protein ◽  
Binding Domain ◽  
Microtubule Binding ◽  
Repeat Structure ◽  
Microtubule Binding Domain

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

scholarly journals Modulation of tau phosphorylation and intracellular localization by cellular stress

2000 ◽  
Vol 345 (2) ◽  
pp. 263-270 ◽  
Author(s):  
Scott M. JENKINS ◽  
Marcus ZINNERMAN ◽  
Craig GARNER ◽  
Gail V. W. JOHNSON
Keyword(s):  
Osmotic Stress ◽  
Protein Kinases ◽  
Intracellular Localization ◽  
Tau Phosphorylation ◽  
Binding Domain ◽  
Microtubule Binding ◽  
Microtubule Binding Domain

Tau is a microtubule-associated protein that is functionally modulated by phosphorylation and hyperphosphorylated in several neurodegenerative diseases. Because phosphorylation regulates both normal and pathological tau functioning, it is of great interest to identify the signalling pathways and enzymes capable of modulating tau phosphorylation in vivo. The present study examined changes in tau phosphorylation and localization in response to osmotic stress, which activates the stress-activated protein kinases (SAPKs), a family of proline-directed protein kinases shown to phosphorylate tau in vitro and hypothesized to phosphorylate tau in Alzheimer's disease. Immunoblot analysis with phosphorylation-dependent antibodies revealed that osmotic stress increased tau phosphorylation at the non-Ser/Thr-Pro sites Ser-262/356, within the microtubule-binding domain, as well as Ser/Thr-Pro sites outside of tau's microtubule-binding domain. Although all SAPKs examined were activated by osmotic stress, none of the endogenous SAPKs mediated the increase in tau phosphorylation. However, when transfected into SH-SY5Y cells, SAPK3, but not the other SAPKs examined, phosphorylated tau in situ in response to activation by osmotic stress. Osmotic-stress-induced tau phosphorylation correlated with a decrease in the amount of tau associated with the cytoskeleton and an increase in the amount of soluble tau. This stress-induced alteration in tau localization was only partially due to phosphorylation at Ser-262/356 by a staurosporine-sensitive, non-proline-directed, protein kinase. Taken together, these results suggest that osmotic stress activates at least two tau-directed protein kinases, one proline-directed and one non-proline-directed, that SAPK3 can phosphorylate tau on Ser/Thr-Pro residues in situ, and that Ser-262/356 phosphorylation only partially regulates tau localization in the cell.

Flavonoids Inhibit Heparin-Induced Aggregation of the Third Repeat (R3) of Microtubule-Binding Domain of Alzheimer’s Tau Protein

2010 ◽  
Vol 83 (8) ◽  
pp. 911-922 ◽  
Author(s):  
Lin-Jie Han ◽  
Shuo Shi ◽  
Leng-Feng Zheng ◽  
Dan-Jing Yang ◽  
Tian-Ming Yao ◽  
...  
Keyword(s):  
Tau Protein ◽  
Binding Domain ◽  
Microtubule Binding ◽  
The Third ◽  
Microtubule Binding Domain ◽  
Induced Aggregation

Importance of Tyr310 residue in the third repeat of microtubule binding domain for filament formation of tau protein

2009 ◽  
Vol 147 (3) ◽  
pp. 405-414 ◽  
Author(s):  
Chisato Nishiura ◽  
Kengo Takeuchi ◽  
Katsuhiko Minoura ◽  
Miho Sumida ◽  
Taizo Taniguchi ◽  
...  
Keyword(s):  
Tau Protein ◽  
Binding Domain ◽  
Filament Formation ◽  
Microtubule Binding ◽  
The Third ◽  
Microtubule Binding Domain

scholarly journals MAP7 family proteins regulate kinesin-1 recruitment and activation

2019 ◽  
Vol 218 (4) ◽  
pp. 1298-1318 ◽  
Author(s):  
Peter Jan Hooikaas ◽  
Maud Martin ◽  
Tobias Mühlethaler ◽  
Gert-Jan Kuijntjes ◽  
Cathelijn A.E. Peeters ◽  
...  
Keyword(s):  
Hela Cells ◽  
Family Members ◽  
Binding Domain ◽  
Allosteric Effect ◽  
Microtubule Binding ◽  
Lower Affinity ◽  
Linker Region ◽  
Microtubule Binding Domain ◽  
Dependent Transport

Kinesin-1 is responsible for microtubule-based transport of numerous cellular cargoes. Here, we explored the regulation of kinesin-1 by MAP7 proteins. We found that all four mammalian MAP7 family members bind to kinesin-1. In HeLa cells, MAP7, MAP7D1, and MAP7D3 act redundantly to enable kinesin-1–dependent transport and microtubule recruitment of the truncated kinesin-1 KIF5B-560, which contains the stalk but not the cargo-binding and autoregulatory regions. In vitro, purified MAP7 and MAP7D3 increase microtubule landing rate and processivity of kinesin-1 through transient association with the motor. MAP7 proteins promote binding of kinesin-1 to microtubules both directly, through the N-terminal microtubule-binding domain and unstructured linker region, and indirectly, through an allosteric effect exerted by the kinesin-binding C-terminal domain. Compared with MAP7, MAP7D3 has a higher affinity for kinesin-1 and a lower affinity for microtubules and, unlike MAP7, can be cotransported with the motor. We propose that MAP7 proteins are microtubule-tethered kinesin-1 activators, with which the motor transiently interacts as it moves along microtubules.

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