MAP7 family proteins regulate kinesin-1 recruitment and activation

Hooikaas, Peter Jan; Martin, Maud; Mühlethaler, Tobias; Kuijntjes, Gert Jan; Peeters, Cathelijn A.E.; Katrukha, Eugene A.; Ferrari, Luca; Stucchi, Riccardo; Verhagen, Daan G.F.; Riel, Wilhelmina E. van; Grigoriev, Ilya; Altelaar, A.F. Maarten; Hoogenraad, Casper C.; Rüdiger, Stefan; Steinmetz, Michel O.; Kapitein, Lukas C.; Akhmanova, Anna

doi:10.1083/jcb.201808065

Cited by 132 publications

(132 citation statements)

References 52 publications

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“…5B). We believe that this stimulation of the motor binding can occur in solution because we were not able to detect any association of the KBD with MTs either in vivo or in vitro, as also recently shown by other groups using rat and human Ensconsin (MAP7) (Hooikaas et al, 2019;Tymanskyj et al, 2018). Interestingly, this interaction between Ensconsin and KHC is observed in cell extracts, with or without polymerized microtubules (this work).…”

Section: Mechanisms Of Ensconsin Stimulation Of Kinesin-1 Recruitmentsupporting

confidence: 60%

“…Second, both proteins colocalize on the internal MT network of Drosophila oocyte egg chambers (Sung et al, 2008, this paper). Third, Ensconsin C-terminal domain (KBD) and Kinesin-1 can interact in vivo (Hooikaas et al, 2019;Metzger et al, 2012, this study). Based on the current literature, the recruitment model suggests that Ensconsin bound to the MT lattice (via the MBD) serves as a direct recruitment platform for Kinesin-1 (Fig.…”

Section: Mechanisms Of Ensconsin Stimulation Of Kinesin-1 Recruitmentmentioning

confidence: 69%

“…We found that both Ensc-GFP and KBD-GFP, but not MBD-GFP, proteins were able to interact with KHC (Fig. 1C, bottom panel), similarly to vertebrate Ensconsin (MAP7) (Hooikaas et al, 2019;Metzger et al, 2012).…”

Section: In Vivo Functional Analysis Of the Different Domains Of Enscmentioning

confidence: 85%

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Dual control of Kinesin-1 recruitment to microtubules by Ensconsin inDrosophilaneuroblasts and oocytes

et al. 2019

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Drosophila Ensconsin (also known as MAP7) controls spindle length, centrosome separation in brain neuroblasts (NBs) and asymmetric transport in oocytes. The control of spindle length by Ensconsin is Kinesin-1 independent but centrosome separation and oocyte transport require targeting of Kinesin-1 to microtubules by Ensconsin. However, the molecular mechanism used for this targeting remains unclear. Ensconsin contains a microtubule (MT)binding domain (MBD) and a Kinesin-binding domain (KBD). Rescue experiments show that only full-length Ensconsin restores the spindle length phenotype. KBD expression rescues ensc centrosome separation defects in NBs, but not the fast oocyte streaming and the localization of Staufen and Gurken. Interestingly, the KBD can stimulate Kinesin-1 targeting to MTs in vivo and in vitro. We propose that a KBD and Kinesin-1 complex is a minimal activation module that increases Kinesin-1 affinity for MTs. Addition of the MBD present in full-length Ensconsin allows this process to occur directly on the MT and triggers higher Kinesin-1 targeting. This dual regulation by Ensconsin is essential for optimal Kinesin-1 targeting to MTs in oocytes, but not in NBs, illustrating the importance of adapting Kinesin-1 recruitment to different biological contexts.

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Section: Mechanisms Of Ensconsin Stimulation Of Kinesin-1 Recruitmentsupporting

confidence: 60%

Section: Mechanisms Of Ensconsin Stimulation Of Kinesin-1 Recruitmentmentioning

confidence: 69%

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Dual control of Kinesin-1 recruitment to microtubules by Ensconsin inDrosophilaneuroblasts and oocytes

et al. 2019

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“…P < 0.0001 (***) using a student's t-test for KIF1A alone vs. KIF1A + MAP7, tau, MAP2, DCX, and DCLK1 and for each MAP combination. P = 0.0034 (**) for KIF1A alone vs. 26,41 . Similarly, prior studies have reported a direct interaction between kinesin-3 and both DCX 46 and DCLK1 6 .…”

Section: Map9 Enables Kinesin-3 Progression On the Lattice Due To A Tmentioning

confidence: 99%

“…In neurons, kinesin-3 and dynein drive various cargoes within both axons and dendrites, while likely that MAP2 affects kinesins and dynein akin to tau. MAP7 is important for a range of kinesin-1 functions in vivo [36][37][38][39][40] , and has been shown in vitro to directly bind and recruit kinesin-1 to the microtubule lattice 26,41,42 . Kinesin-1 is most likely able to navigate the tau-rich axon in part due to the presence of MAP7, which displaces tau from the microtubule 26 .…”

Section: Introductionmentioning

confidence: 99%

A Combinatorial MAP Code Dictates Polarized Microtubule Transport

Monroy

Tan

Oclaman

et al. 2019

Preprint

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Many eukaryotic cells distribute their intracellular components through asymmetrically regulated active transport driven by molecular motors along microtubule tracks. While intrinsic and extrinsic regulation of motor activity exists, what governs the overall distribution of activated motor-cargo complexes within cells remains unclear. Here, we utilize in vitro reconstitution of purified motor proteins and non-enzymatic microtubule-associated proteins (MAPs) to demonstrate that these MAPs exhibit distinct influences on the motility of the three main classes of transport motors: kinesin-1, kinesin-3, and cytoplasmic dynein. Further, we dissect how combinations of MAPs affect motors, and reveal how transient interactions between MAPs and motors may promote these effects. From these data, we propose a general "MAP code" that has the capacity to strongly bias directed movement along microtubules and helps elucidate the intricate intracellular sorting observed in highly polarized cells such as neurons.kinesin-1 carries cargoes into the axon, but is largely excluded from the dendrites 6-10 . Posttranslational modifications of tubulin have been proposed to act as a "tubulin-code" that can be read out by activated motor proteins to direct their movement to specific cellular compartments 9 .However, other than the effect of tyrosination on dynein landing rate 11 , the reported biophysical effects of certain tubulin modifications, such as acetylation, on kinesin motor movement are relatively modest 12 , raising questions about how such effects could directly result in guiding transport in vivo. A large variety of other proteins bind to microtubules, and as such, transport motors must encounter a number of non-enzymatic microtubule-associated proteins (MAPs) that decorate the microtubule cytoskeleton 13 . Disruption of this bidirectional transport system due to mutations in motor complexes or MAPs leads to a wide range of neurodevelopmental and neurodegenerative disorders [13][14][15][16][17] , highlighting the interplay between these classes of proteins.Since the identification of "structural" MAPs that co-purified with polymerized brain tubulin 18 , such as MAP1, MAP2, tau, MAP7, and doublecortin (DCX), MAPs have been described as stabilizers, nucleation-promoting factors, and bundlers of microtubules 19-24 .However, recent work suggests that these MAPs may also function to direct motor transport 6,[25][26][27] . Perhaps the most well-studied MAP with regards to its effects on motors is the Alzheimer's disease-associated MAP, tau, which was originally thought to be axon-specific, but can also be observed in mature dendrites ( Figure S1) 27,28 . Tau inhibits kinesin-1 and kinesin-3 to varying degrees 25,26,29-31 , but does not strongly impede processive dynein motility 27 . These differential effects are due to a steric clash between tau and the relatively large kinesin motor domain, which does not exist for the smaller dynein microtubule-binding domain 27,32,33 . MAP2 is localized to dendrites and the axon initial segment ...

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Optogenetic Control of Myocardin‐Related Transcription Factor A Subcellular Localization and Transcriptional Activity Steers Membrane Blebbing and Invasive Cancer Cell Motility

Zhao

Grosse

2021

Advanced Biology

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Similar to SRF, its coactivator MRTF-A (also known as MAL or MKL1) is ubiquitously expressed and controls actin-associated gene expression for numerous functions in development and disease as well as many cell migratory processes. [3,4] The latter occurs largely via the regulation of cytoskeletal genes following signal-induced MRTF-A nuclear translocation. [5][6][7] Notably, MRTF-A dependent immediate gene expression appears to be the predominant cellular SRF transcriptional response to extracellular signals such as serum. [8] In addition, it is now well established that MRTF-A transcriptional activity is an important driver of tumor progression by promoting invasion and metastasis. [9][10][11][12][13][14][15][16] We could recently show that MRTF-A activity promotes non-apoptotic plasma membrane (PM) blebbing often observed during blebassociated invasive cell migration. [17] This MRTF-A nuclear activity was in turn triggered by PM blebbing thereby facilitating a positive feedback loop to drive PM dynamics and cell motility through MRTF-SRF transcription. [17] Such mechanism is consistent with the fact that nuclear localization of MRTF-A depends on actin dynamics. [5] This occurs via three core RPEL actin-binding sites (R1-R3) and the two spacer actin-binding regions (S1, S2) within the N-terminus of MRTF-A (Figure 1A). [18] Specifically, the RPEL domain of MRTF-A interacts with actin such that binding of all five actin monomers (G-actin) promotes MRTF-A nuclear export while dissociation of the G-actin molecules favors its Nuclear localization signal (NLS)-dependent nuclear import (Figure 1A). [18] This mechanism allows MRTF-A to sense and rapidly respond to changes in actin dynamics resulting in the regulation of gene expression. [19] Nucleocytoplasmic shuttling is regarded as an essential mechanism to control the activity of transcriptional factors. [20] Quite recently, a few optogenetic tools have been generated to artificially manipulate the localization of nuclear proteins, [21] providing a new perspective for modulating cellular activities. Here, we devised and employed an optogenetic strategy using the modified light-oxygen-voltage-sensing domain 2 (LOV2) LEXY to spatiotemporally control MRTF-A nuclear localization and function independently of actin dynamics. Optogenetic The myocardin-related transcription factor A (MRTF-A) controls the transcriptional activity of the serum response factor (SRF) in a tightly controlled actin-dependent manner. In turn, MRTF-A is crucial for many actin-dependent processes including adhesion, migration, and contractility and has emerged as a novel target for anti-tumor strategies. MRTF-A rapidly shuttles between cytoplasmic and nuclear compartment via dynamic actin interactions within its N-terminal RPEL domain.Here, optogenetics is used to spatiotemporally control MRTF-A nuclear localization by blue light using the light-oxygen-voltage-sensing domain 2-domain based system LEXY (light-inducible nuclear export system). It is found that lightregulated nuclear export of MRTF-A o...

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MAP7 family proteins regulate kinesin-1 recruitment and activation

Cited by 132 publications

References 52 publications

Dual control of Kinesin-1 recruitment to microtubules by Ensconsin inDrosophilaneuroblasts and oocytes

Dual control of Kinesin-1 recruitment to microtubules by Ensconsin inDrosophilaneuroblasts and oocytes

A Combinatorial MAP Code Dictates Polarized Microtubule Transport

Optogenetic Control of Myocardin‐Related Transcription Factor A Subcellular Localization and Transcriptional Activity Steers Membrane Blebbing and Invasive Cancer Cell Motility

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