Shootin1–cortactin interaction mediates signal–force transduction for axon outgrowth

Kubo, Yusuke; Baba, Kenichiro; Toriyama, Minoru; Minegishi, Takunori; Sugiura, T.; Kozawa, Satoshi; Ikeda, Kazushi; Inagaki, Naoyuki

doi:10.1083/jcb.201505011

Cited by 65 publications

(116 citation statements)

References 63 publications

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“…These mass spectrometry data confirm that SHOT1 is phosphorylated by YopO at Ser249, which contains the canonical PAK phosphorylation sequence (K/R-R-X-p[S/T])26. Given the structural similarity of YopO’s kinase domain with PAKs, we assayed whether PAKs (in this case PAK4) can phosphorylate other substrates of YopO (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 65%

“…PKD1 phosphorylates VASP at Ser153 and Ser319 (numbering for mouse, Ser157 and Ser322 in human), and in contrast, increases F-actin polymerization and reduces VASP localization at focal adhesions43. YopO phosphorylates SHOT1 at Ser249, which is also targeted by PAK1, and results in enhancing SHOT1’s interaction with cortactin at sites of dynamic actin assembly26.…”

Section: Discussionmentioning

confidence: 99%

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Mechanisms of Yersinia YopO kinase substrate specificity

Lee

Singaravelu

Wee

et al. 2017

Sci Rep

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Yersinia bacteria cause a range of human diseases, including yersiniosis, Far East scarlet-like fever and the plague. Yersiniae modulate and evade host immune defences through injection of Yersinia outer proteins (Yops) into phagocytic cells. One of the Yops, YopO (also known as YpkA) obstructs phagocytosis through disrupting actin filament regulation processes - inhibiting polymerization-promoting signaling through sequestration of Rac/Rho family GTPases and by using monomeric actin as bait to recruit and phosphorylate host actin-regulating proteins. Here we set out to identify mechanisms of specificity in protein phosphorylation by YopO that would clarify its effects on cytoskeleton disruption. We report the MgADP structure of Yersinia enterocolitica YopO in complex with actin, which reveals its active site architecture. Using a proteome-wide kinase-interacting substrate screening (KISS) method, we identified that YopO phosphorylates a wide range of actin-modulating proteins and located their phosphorylation sites by mass spectrometry. Using artificial substrates we clarified YopO’s substrate length requirements and its phosphorylation consensus sequence. These findings provide fresh insight into the mechanism of the YopO kinase and demonstrate that YopO executes a specific strategy targeting actin-modulating proteins, across multiple functionalities, to compete for control of their native phospho-signaling, thus hampering the cytoskeletal processes required for macrophage phagocytosis.

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Section: Resultsmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Mechanisms of Yersinia YopO kinase substrate specificity

Lee

Singaravelu

Wee

et al. 2017

Sci Rep

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“…[27] As discussed earlier, additional folic acid increased the expression of a marker of neuronal differentiation, microtubule-associated protein 2 (MAP-2), in PC-12 cells. Here, we explored whether the chemical stimuli by folic acid would not only increase the expression of cytoskeletal filaments such as microtubules, but also lead to higher cytoskeletal tension, thus increasing cellular traction forces.…”

Section: Resultsmentioning

confidence: 98%

The critical chemical and mechanical regulation of folic acid on neural engineering

et al. 2018

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The mandate of folic acid supplementation in grained products has reduced the occurrence of neural tube defects by one third in the U.S since its introduction by the Food and Drug Administration in 1998. However, the advantages and possible mechanisms of action of using folic acid for peripheral nerve engineering and neurological diseases still remain largely elusive. Herein, folic acid is described as an inexpensive and multifunctional niche component that modulates behaviors in different cells in the nervous system. The multiple benefits of modulation include: 1) generating chemotactic responses on glial cells, 2) inducing neurotrophin release, and 3) stimulating neuronal differentiation of a PC-12 cell system. For the first time, folic acid is also shown to enhance cellular force generation and global methylation in the PC-12 cells, thereby enabling both biomechanical and biochemical pathways to regulate neuron differentiation. These findings are evaluated in vivo for clinical translation. Our results suggest that folic acid-nerve guidance conduits may offer significant benefits as a low-cost, off-the-shelf product for reaching the functional recovery seen with autografts in large sciatic nerve defects. Consequently, folic acid holds great potential as a critical and convenient therapeutic intervention for neural engineering, regenerative medicine, medical prosthetics, and drug delivery.

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“…Growth cones exhibit F-actin RF similar to cells migrating on ECM [51–53] and clutching of RF is thought to regulate the rate and direction of axon extension [54–59]. Evidence from several laboratories has shown that the rate of RF is directly related to substratum traction forces [60–62] and inversely related to the rate of growth cone advance [54, 63].…”

Section: Growth Cone Point Contact (Pc) Adhesions Regulate Axon Outgrmentioning

confidence: 99%

Cell adhesion and invasion mechanisms that guide developing axons

Short

Suarez-Zayas

Gómez

2016

Current Opinion in Neurobiology

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Axon extension, guidance and tissue invasion share many similarities to normal cell migration and cancer cell metastasis. Proper cell and growth cone migration requires tightly regulated adhesion complex assembly and detachment from the extracellular matrix (ECM). In addition, many cell types actively remodel the ECM using matrix metalloproteases (MMPs) to control tissue invasion and cell dispersal. Targeting and activating MMPs is a tightly regulated process, that when dysregulated, can lead to cancer cell metastasis. Interestingly, new evidence suggests that growth cones express similar cellular and molecular machinery as migrating cells to clutch retrograde actin flow on ECM proteins and target matrix degradation, which may be used to facilitate axon pathfinding through the basal lamina and across tissues.

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Shootin1–cortactin interaction mediates signal–force transduction for axon outgrowth

Abstract: The shootin1–cortactin interaction participates in netrin-1–induced F-actin–adhesion coupling and in the promotion of traction forces for axon outgrowth.

Cited by 65 publications

References 63 publications

Mechanisms of Yersinia YopO kinase substrate specificity

Mechanisms of Yersinia YopO kinase substrate specificity

The critical chemical and mechanical regulation of folic acid on neural engineering

Cell adhesion and invasion mechanisms that guide developing axons

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