Mercury(II) promotes the in vitro aggregation of tau fragment corresponding to the second repeat of microtubule-binding domain: Coordination and conformational transition

Biopolymers ◽  
2010 ◽  
Vol 93 (12) ◽  
pp. 1100-1107 ◽  
Author(s):  
Dan-Jing Yang ◽  
Shuo Shi ◽  
Leng-Feng Zheng ◽  
Tian-Ming Yao ◽  
Liang-Nian Ji
Keyword(s):  
Conformational Transition ◽  
Binding Domain ◽  
Microtubule Binding ◽  
Microtubule Binding Domain

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.

Structural evaluation of conformational transition state responsible for self-assembly of tau microtubule-binding domain

2005 ◽  
Vol 327 (4) ◽  
pp. 1100-1104 ◽  
Author(s):  
Katsuhiko Minoura ◽  
Fumie Mizushima ◽  
Mari Tokimasa ◽  
Shuko Hiraoka ◽  
Koji Tomoo ◽  
...  
Keyword(s):  
Transition State ◽  
Self Assembly ◽  
Conformational Transition ◽  
Binding Domain ◽  
Microtubule Binding ◽  
Structural Evaluation ◽  
Microtubule Binding Domain

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 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.

scholarly journals Stress-induced phosphorylation of CLIP-170 by JNK promotes microtubule rescue

2020 ◽  
Vol 219 (7) ◽  
Author(s):  
Hélène Henrie ◽  
Dalal Bakhos-Douaihy ◽  
Isabelle Cantaloube ◽  
Antoine Pilon ◽  
Maya Talantikite ◽  
...  
Keyword(s):  
Binding Domain ◽  
Cell Stress ◽  
Microtubule Dynamics ◽  
Microtubule Binding ◽  
Microtubule Binding Domain ◽  
Microtubule Growth ◽  
Jnk Activation ◽  
In Cells

The stress-induced c-Jun N-terminal kinase (JNK) controls microtubule dynamics by enhancing both microtubule growth and rescues. Here, we show that upon cell stress, JNK directly phosphorylates the microtubule rescue factor CLIP-170 in its microtubule-binding domain to increase its rescue-promoting activity. Phosphomimetic versions of CLIP-170 enhance its ability to promote rescue events in vitro and in cells. Furthermore, while phosphomimetic mutations do not alter CLIP-170’s capability to form comets at growing microtubule ends, both phosphomimetic mutations and JNK activation increase the occurrence of CLIP-170 remnants on the microtubule lattice at the rear of comets. As the CLIP-170 remnants, which are potential sites of microtubule rescue, display a shorter lifetime when CLIP-170 is phosphorylated, we propose that instead of acting at the time of rescue occurrence, CLIP-170 would rather contribute in preparing the microtubule lattice for future rescues at these predetermined sites.

Characterization of the microtubule binding domain of microtubule actin crosslinking factor (MACF): identification of a novel group of microtubule associated proteins

2001 ◽  
Vol 114 (1) ◽  
pp. 161-172 ◽  
Author(s):  
D. Sun ◽  
C.L. Leung ◽  
R.K. Liem
Keyword(s):  
Calcium Binding ◽  
Binding Domain ◽  
Actin Binding ◽  
Microtubule Binding ◽  
Transfected Cells ◽  
Terminal Domain ◽  
Microtubule Binding Domain

MACF (microtubule actin cross-linking factor) is a large, 608-kDa protein that can associate with both actin microfilaments and microtubules (MTs). Structurally, MACF can be divided into 3 domains: an N-terminal domain that contains both a calponin type actin-binding domain and a plakin domain; a rod domain that is composed of 23 dystrophin-like spectrin repeats; and a C-terminal domain that includes two EF-hand calcium-binding motifs, as well as a region that is homologous to two related proteins, GAR22 and Gas2. We have previously demonstrated that the C-terminal domain of MACF binds to MTs, although no homology was observed between this domain and other known microtubule-binding proteins. In this report, we describe the characterization of this microtubule-binding domain of MACF by transient transfection studies and in vitro binding assays. We found that the C-terminus of MACF contains at least two microtubule-binding regions, a GAR domain and a domain containing glycine-serine-arginine (GSR) repeats. In transfected cells, the GAR domain bound to and partially stabilized MTs to depolymerization by nocodazole. The GSR-containing domain caused MTs to form bundles that are still sensitive to nocodazole-induced depolymerization. When present together, these two domains acted in concert to bundle MTs and render them stable to nocodazole treatment. Recently, a study has shown that the N-terminal half of the plakin domain (called the M1 domain) of MACF also binds MTs. We therefore examined the microtubule binding ability of the M1 domain in the context of the entire plakin domain with and without the remaining N-terminal regions of two different MACF isoforms. Interestingly, in the presence of the surrounding sequences, the M1 domain did not bind MTs. In addition to MACF, cDNA sequences encoding the GAR and GSR-containing domains are also found in the partial human EST clone KIAA0728, which has high sequence homology to the 3′ end of the MACF cDNA; hence, we refer to it as MACF2. The C-terminal domain of mouse MACF2 was cloned and characterized. The microtubule-binding properties of MACF2 C-terminal domain are similar to that of MACF. The GAR domain was originally found in Gas 2 protein and here we show that it can associate with MTs in transfected cells. Plectin and desmoplakin have GSR-containing domains at their C-termini and we further demonstrate that the GSR-containing domain of plectin, but not desmoplakin, can bind to MTs in vivo.

Phosphorylation of MAP4 affects microtubule properties and cell cycle progression

2001 ◽  
Vol 114 (15) ◽  
pp. 2879-2887 ◽  
Author(s):  
Winston Chang ◽  
Dorota Gruber ◽  
Sripriya Chari ◽  
Hidefumi Kitazawa ◽  
Yuko Hamazumi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Binding Domain ◽  
Proliferating Cells ◽  
Cycle Progression ◽  
Microtubule Binding ◽  
Microtubule Binding Domain ◽  
In Cells

In human cells, MAP4, a microtubule-associated protein ubiquitously expressed in proliferating cells, has been shown to undergo in vivo phosphorylation. Two phosphorylation sites, serines 696 and 787, lie within the proline-rich region of its microtubule-binding domain. To test the hypothesis that phosphorylation at these sites influences microtubule properties or cell cycle progression, we prepared stable cell lines that inducibly express versions of MAP4 in which phosphorylation of these two serines was prevented by their replacement with alanine, lysine, or glutamate residues (AA-, KK-, or EE-MAP4). All non-phosphorylatable mutant forms of MAP4 expressed in mouse Ltk- cells were localized to MT arrays that were unremarkable in appearance. Expression of non-phosphorylatable mutants of MAP4 did not affect cell doubling time; however, expression of some mutants altered progression into or through cell division. Interactions of mutant MAP4 with MTs were examined in vitro. KK mutant MAP4 bound MTs more avidly than its wild-type counterpart, WT-MAP4. In vivo MT polymer also differed among the mutants: MTs in cells expressing the KK- and AA-MAP4 forms were more resistant to nocodazole depolymerization than those in cells expressing EE- or WT-MAP4 forms. Our results demonstrate that phosphorylation alters MAP4 properties and suggest a raison d'être for phosphorylation of the MAP4 microtubule-binding domain during cell cycle progression.

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