Map7/7D1 and Dvl form a feedback loop that facilitates microtubule remodeling and Wnt5a signaling

Kikuchi, Koji; Nakamura, Akira; Arata, Masaki; Shi, Dongbo; Nakagawa, Mami; Tanaka, Tsubasa; Uemura, Tadashi; Fujimori, Toshihiko; Kikuchi, Akira; Uezu, Akiyoshi; Sakamoto, Yasuhisa; Nakanishi, Hiroyuki

doi:10.15252/embr.201745471

Cited by 19 publications

(35 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MAP7D3 can be rapidly relocalized to MT plus ends by overexpressed K560, but at the endogenous kinesin-1 expression levels, MAP7D3 is not enriched at MT plus ends, suggesting that the levels of endogenous motor are insufficient to drive MAP7D3 to the cell periphery. Still, it is possible that also the endogenous kinesin-1 could cause some redistribution of its own positive regulators, which would be in line with some previous observations (Kikuchi et al, 2018).…”

Section: Discussionsupporting

confidence: 89%

MAP7 family proteins regulate kinesin-1 recruitment and activation

Hooikaas

Martin

Mühlethaler

et al. 2019

Journal of Cell Biology

133

112

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 89%

MAP7 family proteins regulate kinesin-1 recruitment and activation

Hooikaas

Martin

Mühlethaler

et al. 2019

Journal of Cell Biology

133

112

View full text Add to dashboard Cite

show abstract

“…1A, B). Gene expression analysis at the mRNA and protein level indicated that HeLa cells co-express MAP7, MAP7D1 and MAP7D3 (Kikuchi et al, 2018;Syred et al, 2013), and we confirmed these data by antibody staining (Fig. 1C).…”

Section: Map7 Family Members Act Redundantly In Mitochondrial Distribsupporting

confidence: 85%

MAP7 family proteins regulate kinesin-1 recruitment and activation

Hooikaas

Martin

Mühlethaler

et al. 2018

Preprint

View full text Add to dashboard Cite

Kinesin-1 is responsible for microtubule-based transport of numerous cellular cargoes. Here, we explored the regulation of kinesin-1 by MAP7/ensconsin family proteins. We found that all four mammalian MAP7 family members bound to kinesin-1, and MAP7, MAP7D1 and MAP7D3 acted redundantly to enable kinesin-1-dependent transport in HeLa cells. Microtubule recruitment of the truncated kinesin-1 KIF5B-560, which contains the stalk but not the cargo-binding and autoregulatory regions, was inhibited in cells co-depleted of these three MAP7 proteins. In vitro, purified MAP7 and MAP7D3 increased microtubule landing rate and processivity of KIF5B-560.The same was true for MAP7D3 C-terminus, which weakly bound to microtubules and exchanged rapidly on motile KIF5B-560 motors. A C-terminal MAP7 fragment lacking microtubule affinity increased KIF5B-560 recruitment to microtubules in vitro and in cells, and partially rescued kinesin-1-dependent transport in the absence of full-length MAP7 proteins. We propose that MAP7 proteins are microtubule-tethered kinesin-1 activators, with which the motor transiently interacts as it moves along microtubules. SummaryA combination of experiments in cells and in vitro reconstitution assays demonstrated that mammalian MAP7 family proteins act redundantly to activate kinesin-1 and promote its microtubule binding and processivity by transiently associating with the stalk region of the motor.All rights reserved. No reuse allowed without permission.was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

show abstract

“…Map7/7D1 binds to Dvl and modulates MT remodeling in HeLa cells, whereas Map7/7D1 knockdown impaired MT plus-end cortical targeting and focal adhesion turnover. Furthermore, Map7/7D1 promotes the cortical targeting of Dvl in response to Wnt5a, providing further support to the role of Dvl in cell migration dynamics during Wnt5a signaling (Kikuchi et al, 2018). However, it must be stressed that the specific relevance of these findings for gastric cancer remains to be fully explored.…”

Section: Wnt5a In Gastric Cancer: Molecular Mechanismsmentioning

confidence: 80%

Wnt5a Signaling in Gastric Cancer

Astudillo

2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Gastric cancer remains an important health challenge, accounting for a significant number of cancer-related deaths worldwide. Therefore, a deeper understanding of the molecular mechanisms involved in gastric cancer establishment and progression is highly desirable. The Wnt pathway plays a fundamental role in development, homeostasis, and disease, and abnormal Wnt signaling is commonly observed in several cancer types. Wnt5a, a ligand that activates the non-canonical branch of the Wnt pathway, can play a role as a tumor suppressor or by promoting cancer cell invasion and migration, although the molecular mechanisms explaining these roles have not been fully elucidated. Wnt5a is increased in gastric cancer samples; however, most gastric cancer cell lines seem to exhibit little expression of this ligand, thus raising the question about the source of this ligand in vivo. This review summarizes available research about Wnt5a expression and signaling in gastric cancer. In gastric cancer, Wnt5a promotes invasion and migration by modulating integrin adhesion turnover. Disheveled, a scaffolding protein with crucial roles in Wnt signaling, mediates the adhesion-related effects of Wnt5a in gastric cancer cells, and several studies provide growing support for a model whereby Disheveled-interacting proteins mediates Wnt5a signaling to modulate cytoskeleton dynamics. However, Wnt5a might induce other effects in gastric cancer cells, such as cell survival and induction of gene expression. On the other hand, the available evidence suggests that Wnt5a might be expressed by cells residing in the tumor microenvironment, where feedback mechanisms sustaining Wnt5a secretion and signaling might be established. This review analyzes the possible functions of Wnt5a in this pathological context and discusses potential links to mechanosensing and YAP/TAZ signaling.

show abstract

Map7/7D1 and Dvl form a feedback loop that facilitates microtubule remodeling and Wnt5a signaling

Cited by 19 publications

References 59 publications

MAP7 family proteins regulate kinesin-1 recruitment and activation

MAP7 family proteins regulate kinesin-1 recruitment and activation

MAP7 family proteins regulate kinesin-1 recruitment and activation

Wnt5a Signaling in Gastric Cancer

Contact Info

Product

Resources

About