Regulation of Microtubule Cytoskeleton (Homo sapiens)

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1, 2MicrotubulePlus EndPlus End ProteinsMT StabilityFocal AdhesionActin FilamentsMT CatastropheDelivery toMT Plus EndsMT PolymerizationNeurotrophinsPIP3+ end GrowthPromoting+/- endDestabilizingRTKMinus End"DynamicMicrotubules"RhoTAULL5خ²TPPPLIMK*TESK*MAPKAPK*DVL*PKC*PAR6*TAOK*SPRED1ROCK*RAC1MARKCFL*GSK3BMARK2PAR3PAR1*PTENAKT*ERKCDC42PIK3*GNAQ WNT*LPRSTAT3STMN*PAK*PRKACAAURKBCAMK*CDK1MCAKXMAP215*ICIS*RhoGEFc-ABLTRIOTIAM1SRCCLASP*CLIP*MAP1BCRMP2EB1APCmDIA*mDIA*EB1CLIP*CLIP*CLIP*CLASP*EB1APCRAC1RhomDIA1*GNAQ RhoRhoMAP1BERKPIP3


Description

Microtubules are required for the establishment of cell polarity, polarized migration of cells, intracellular vesicle transport, and chromosomal segregation in mitosis. Microtubules (MTs) are nonequilibrium polymers of α/β-tubulin heterodimers, in which GTP hydrolysis on the β-tubulin subunit occurs following assembly. Most microtubules are nucleated from organizing centers. The most prevalent microtubule behavior is dynamic instability, a process of slow plus end growth coupled with rapid depolymerization (“catastrophe”) and subsequent rescue. Although microtubule minus ends show dynamic instability, albeit at a lower rate than the plus ends, the minus ends are usually capped and anchored at MT organizing centers and thus often do not participate in microtubule dynamics.

Maintaining a balance between dynamically unstable and stable microtubules is regulated in large part by proteins that bind either tubulin dimers or assembled microtubules. Proteins that bind tubulin dimers include stathmin, which sequesters tubulin and enhances MT dynamics by increasing catastrophe frequency, and collapsin response mediator protein (CRMP2), which increases MT growth rate by promoting addition of tubulin dimers onto microtubule plus ends. Other proteins that associate with assembled MTs include those that bundle MTs (e.g. MAP1c), those that stabilize MTs (e.g. tau), and those that maintain MTs in a dynamic state (MAP1b). A major signaling pathway that regulates MT dynamics involves GSK-3β, a kinase typically active under basal growth conditions but locally inactive in response to signals that enhance MT growth and dynamics.

In addition to the above factors, many MT motor proteins, and even non-motor proteins, aid in the dynamics of MTs. Proteins such as Xenopus microtubule associated protein 215 (XMAP215), promote MT assembly through binding to tubulin dimer to facilitate its incorporation in the growing plus end. XMAP215 also may compete with some of the MT plus end binding proteins (+TIPS), of which the end binding protein EB1 appears to be the master organizer. Complexes between the adenomateous polyposis coli (APC) protein and plus end binding proteins stabilize MTs by increasing the duration of the MT elongation phase. MT instability is promoted by several nonmotile kinesins from the kinesin-13 family. The mitotic centromere associated kinesin, MCAK, one of the most studied kinesin-13 family proteins, binds both plus and minus MT ends in vitro. The binding of MCAK to a MT end is thought to accelerate the transition to catastrophe by weakening the lateral interactions between the protofilaments.

Tubulin undergoes several post-translational modifications such as acetylation, polyglutamylation, and poly-glycylation, which have been shown to alter the association with certain MT motors as well as other proteins that can affect MT stability and dynamics.

Source: https://www.cellsignal.com/contents/science-pathway-research-cytoskeletal/regulation-of-microtubule-dynamics-signaling-pathway/pathways-micro

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Bibliography

  1. Etienne-Manneville S; ''From signaling pathways to microtubule dynamics: the key players.''; Curr Opin Cell Biol, 2010 PubMed
  2. Anitei M, Hoflack B; ''Bridging membrane and cytoskeleton dynamics in the secretory and endocytic pathways.''; Nat Cell Biol, 2011 PubMed

History

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94910view23:58, 12 October 2017Khanspersconnected interactions
94754view15:29, 5 October 2017Mkutmonfix unconnected line
90889view22:33, 15 December 2016Khanspersadded lit refs
90888view22:30, 15 December 2016Khanspersfilled in missing parts, updated unconnected etc
90699view01:24, 13 December 2016KhanspersModified description
87632view08:54, 25 July 2016LindarieswijkOntology Term : 'cell-extracellular matrix signaling pathway' added !
79994view20:37, 29 April 2015ZariAnnotated PAR3, mDIA*
78570view14:50, 7 January 2015MaintBotadded missing graphIds
70100view18:46, 12 July 2013MaintBotupdated to 2013 schema
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47074view00:04, 15 March 2012KhanspersModified categories
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External references

DataNodes

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NameTypeDatabase referenceComment
AKT*GeneProductENSG00000142208 (Ensembl)
APCGeneProductENSG00000134982 (Ensembl)
AURKBGeneProductENSG00000178999 (Ensembl)
CAMK*GeneProductENSG00000152495 (Ensembl)
CDC42GeneProductENSG00000070831 (Ensembl)
CDK1GeneProductENSG00000170312 (Ensembl)
CFL*GeneProductENSG00000165410 (Ensembl)
CLASP*GeneProductENSG00000074054 (Ensembl)
CLIP*GeneProductENSG00000130779 (Ensembl)
CRMP2GeneProductENSG00000092964 (Ensembl)
DVL*GeneProductENSG00000107404 (Ensembl)
EB1GeneProductENSG00000101367 (Ensembl)
ERKGeneProductENSG00000133216 (Ensembl)
GNAQ GeneProductENSG00000156052 (Ensembl)
GSK3BGeneProductENSG00000082701 (Ensembl)
ICIS*GeneProduct
LIMK*GeneProductENSG00000106683 (Ensembl)
LL5خ²GeneProductENSG00000144824 (Ensembl)
LPRGeneProductENSG00000132670 (Ensembl)
MAP1BGeneProductENSG00000131711 (Ensembl)
MAPKAPK*GeneProductENSG00000162889 (Ensembl)
MARK2GeneProductENSG00000072518 (Ensembl)
MARKGeneProductENSG00000116141 (Ensembl)
MCAKGeneProductENSG00000142945 (Ensembl)
PAK*GeneProductENSG00000149269 (Ensembl)
PAR1*GeneProductENSG00000072518 (Ensembl)
PAR3GeneProduct2151 (Entrez Gene)
PAR6*GeneProductENSG00000102981 (Ensembl)
PIK3*GeneProductENSG00000121879 (Ensembl)
PKC*GeneProductENSG00000154229 (Ensembl)
PRKACAGeneProductENSG00000072062 (Ensembl)
PTENGeneProductENSG00000171862 (Ensembl)
RAC1GeneProductENSG00000136238 (Ensembl)
ROCK*GeneProductENSG00000067900 (Ensembl)
RhoGeneProductENSG00000163914 (Ensembl)
RhoGEFGeneProduct
SPRED1GeneProductENSG00000166068 (Ensembl)
SRCGeneProductENSG00000197122 (Ensembl)
STAT3GeneProductENSG00000168610 (Ensembl)
STMN*GeneProductENSG00000117632 (Ensembl)
TAOK*GeneProductENSG00000160551 (Ensembl)
TAUGeneProductENSG00000186868 (Ensembl)
TESK*GeneProductENSG00000070759 (Ensembl)
TIAM1GeneProductENSG00000156299 (Ensembl)
TPPPGeneProductENSG00000171368 (Ensembl)
TRIOGeneProductENSG00000038382 (Ensembl)
WNT*GeneProductENSG00000154342 (Ensembl)
XMAP215*GeneProduct
c-ABLGeneProductENSG00000097007 (Ensembl)
mDIA*GeneProduct1729 (Entrez Gene)
mDIA1*GeneProduct1729 (Entrez Gene)

Annotated Interactions

No annotated interactions

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