SLAIN2 links microtubule plus end–tracking proteins and controls microtubule growth in interphase

Vaart, Babet van der; Manatschal, Cristina; Grigoriev, Ilya; Oliéric, V.; Gouveia, Susana Montenegro; Bjelić, Saša; Demmers, Jeroen; Vorobjev, Ivan A.; Hoogenraad, Casper C.; Steinmetz, Michel O.; Akhmanova, Anna

doi:10.1083/jcb.201012179

Cited by 126 publications

(150 citation statements)

References 48 publications

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“…Because Centralspindlin is a heterotetrameric complex (Mishima et al, 2002) and forms higher-order clusters that are important for its function (Hutterer, Glotzer, and Mishima, 2009), it is possible that multiple SxIP motifs within Centralspindlin clusters may facilitate its association with EBs in cells. Indeed, the presence of multiple SxIP motifs that mediate binding to EBs has been noted in other +TIP proteins (Applewhite et al, 2010;Buey et al, 2012;Honnappa et al, 2009;van der Vaart et al, 2011). Interestingly, we found that although mutation of the Mgc SxIP motif strongly reduces the ability of Mgc to track with EB3, the mutant Mgc still affected the EB3 run time along MTs.…”

Section: Discussionsupporting

confidence: 55%

The MgcRacGAP SxIP motif tethers Centralspindlin to microtubule plus ends in Xenopus laevis

Breznau

Murt

Blasius

et al. 2017

Journal of Cell Science

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Centralspindlin, a complex of the kinesin-6-family member MKLP1 and MgcRacGAP (also known as Kif23 and Racgap1, respectively), is required for cytokinesis and cell-cell junctions. During anaphase, Centralspindlin accumulates at overlapping central spindle microtubules and directs contractile ring formation by recruiting the GEF Ect2 to the cell equator to activate RhoA. We found that MgcRacGAP localized to the plus ends of equatorial astral microtubules during cytokinesis in Xenopus laevis embryos. How MgcRacGAP is stabilized at microtubule plus ends is unknown. We identified an SxIP motif in X. laevis MgcRacGAP that is conserved with other proteins that bind to EB1 (also known as Mapre1), a microtubule plus-end tracking protein. Mutation of the SxIP motif in MgcRacGAP resulted in loss of MgcRacGAP tracking with EB3 (also known as Mapre3) on growing microtubule plus ends, abnormal astral microtubule organization, redistribution of MgcRacGAP from the contractile ring to the polar cell cortex, and mislocalization of RhoA and its downstream targets, which together contributed to severe cytokinesis defects. Furthermore, mutation of the MgcRacGAP SxIP motif perturbed adherens junctions. We propose that the MgcRacGAP SxIP motif is functionally important both for its role in regulating adherens junction structure during interphase and for regulating Rho GTPase activity during cytokinesis.

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Section: Discussionsupporting

confidence: 55%

The MgcRacGAP SxIP motif tethers Centralspindlin to microtubule plus ends in Xenopus laevis

Breznau

Murt

Blasius

et al. 2017

Journal of Cell Science

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“…Our past (15) and present results support the emerging concept that serine and threonine phosphorylation in the SXIP flanking regions is used in cells to destabilize the SXIP-EB complex and probably also the interaction with microtubules through an electrostatic repulsion effect. Prominent examples of ϩTIPs that are regulated by phosphorylation within their MtLS sequences include MCAK (15), CLASP (16), APC (7), and SLAIN2 (21).…”

Section: Discussionmentioning

confidence: 99%

“…We and others recently found that multiple SXIP motifs can act in concert to enhance microtubule tip localization in cells (15,21,40). To assess the effect of multiple SXIP motifs, we investigated the S. cerevisiae ϩTIP Ipl1p (24, 25), which contains two consecutive SXIP motifs (Fig.…”

Section: Binding Of Different Sxip-containing ϩTip Fragments To Ebs Amentioning

confidence: 99%

Sequence Determinants of a Microtubule Tip Localization Signal (MtLS)

Buey

Sen

Kortt

et al. 2012

Journal of Biological Chemistry

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Background: Microtubule plus-end-tracking proteins (ϩTIPs) use microtubule tip localization signals (MtLSs) to target growing microtubule ends in an end-binding protein (EB)-dependent manner. Results: The data define the sequence determinants of a canonical MtLS. Conclusion: EB binding affinity and microtubule-tip tracking activity correlate. Significance: The data provide a basis to carry out genome-wide predictions of novel ϩTIPs.

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“…Family members utilize characteristic domains to localize to MT plus-ends and promote MT polymerization. XMAP215 family members have a conserved C-terminal domain that binds SLAIN2 (H. sapiens)/Sentin (D. melanogaster), which confers EB1-dependent MT plus-end localization (33,34). EB1 fenestrates the MT lattice, binding between four tubulin heterodimers where it recognizes tubulin in a GTP hydrolysis transition/post-hydrolysis state mimicked by the GTP analog GTP␥S (58 -60).…”

Section: Discussionmentioning

confidence: 99%

Drosophila melanogaster Mini Spindles TOG3 Utilizes Unique Structural Elements to Promote Domain Stability and Maintain a TOG1- and TOG2-like Tubulin-binding Surface

Howard

Fox

Slep

2015

Journal of Biological Chemistry

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Background: XMAP215 family members contain arrayed TOG domains that promote microtubule polymerization. Results: TOG3 has a unique architecture that positions conserved residues in a TOG1-and TOG2-like tubulin-binding mode. Conclusion: TOG1, TOG2, and TOG3 have similar architectures and predicted tubulin-binding modes that contrast with TOG4. Significance: XMAP215 family members use a structurally diverse, polarized TOG domain array to promote microtubule polymerization.

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SLAIN2 links microtubule plus end–tracking proteins and controls microtubule growth in interphase

Abstract: SLAIN2’s interactions with multiple different microtubule plus end–tracking proteins stimulate processive microtubule polymerization and ensure proper microtubule organization.

Cited by 126 publications

References 48 publications

The MgcRacGAP SxIP motif tethers Centralspindlin to microtubule plus ends in Xenopus laevis

The MgcRacGAP SxIP motif tethers Centralspindlin to microtubule plus ends in Xenopus laevis

Sequence Determinants of a Microtubule Tip Localization Signal (MtLS)

Drosophila melanogaster Mini Spindles TOG3 Utilizes Unique Structural Elements to Promote Domain Stability and Maintain a TOG1- and TOG2-like Tubulin-binding Surface

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