Microtubule cytoskeleton regulation (Homo sapiens)

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1, 2MicrotubuleFocal adhesionActin filaments+/- enddestabilizingPlus end proteinsMinus endPlus endMT stabilityNeurotrophinsMT catastropheDelivery toMT plus endsMT polymerization+ end growthpromoting"Dynamicmicrotubules"PIP3RHOMAPTLL5bTPPPLIMKTESKMAPKAPK2DVL1PKCPAR6TAOKSPRED1ROCKRAC1MARKCFLGSK3BMARK2PAR3PAR1PTENAKTERKCDC42GNAQ WNTLPRSTAT3STMN1PAKPRKACAAURKBCAMKCDK1MCAKXMAP215ICISRhoGEFABL1TRIOTIAM1SRCCLASPCLIPMAP1BCRMP2MAPRE1APCDIAPH1DIAPH1MAPRE1CLIPCLIPCLIPCLASPMAPRE1APCRAC1RHODIAPH1GNAQ RHORHOMAP1BERKPI3KPIP3NTRK1NTRK2NTRK3


Description

Microtubules (MTs) are essential for vesicle transport, cellular polarity and the segregation of chromosomes during mitosis.

MTs are dynamic, undergoing assembly and depolymerization (primarily at the "plus end") by processes actively regulated by signaling pathways. The tubulin dimers that constitute MTs (depicted in green) are bound and sequestered by stathmin (STMN1), enhancing MT dynamics by increasing rapid depolymerization (a.k.a., "MT catastrophe").

MT dynamics are also enhanced by collapsin response mediator protein (CRMP2), which increases MT growth by promoting the addition of tubulin dimers onto microtubule plus ends. Other proteins that associate with assembled MTs include those that stabilize MTs (e.g. tau or MAPT), those that promote assembly (e.g., XMAP215), and those that maintain MTs in a dynamic state (e.g., MAP1B). Complexes between the adenomateous polyposis coli (APC) protein and plus end binding proteins (e.g., EB1) stabilize MTs by increasing the duration of the MT elongation phase. MT instability is promoted by several nonmotile kinesins from the kinesin-13 family, e.g., the mitotic centromere associated kinesin, MCAK, by accelerating the transition to catastrophe by weakening the lateral interactions between the protofilaments.

Upstream from these processes, major signaling pathways act to regulate MT dynamics, e.g., those converging on GSK3B, a kinase which targets tau and CRMP2.

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

Proteins on this pathway have targeted assays available via the CPTAC Assay Portal

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Ontology Terms

 

Bibliography

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

History

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CompareRevisionActionTimeUserComment
134122view19:34, 24 June 2024Khanspersimprove layout
134120view23:49, 21 June 2024Khanspersungroup NTRKs from PI3K
134119view23:26, 21 June 2024Khanspersaswitched RTK node for three nodes representing trk family proteins
129877view11:53, 23 May 2024EweitzModified description
129876view11:53, 23 May 2024EweitzModified description
129875view11:53, 23 May 2024EweitzModified description
129874view11:52, 23 May 2024EweitzModified description
129873view11:50, 23 May 2024EweitzModified description
129872view11:48, 23 May 2024EweitzUse official gene symbol
129871view11:46, 23 May 2024EweitzUpgrade PIP3 to identified metabolite node
129870view11:40, 23 May 2024EweitzUse standard gene symbols
129869view11:37, 23 May 2024EweitzFix gene symbol, use Ensembl
129847view03:20, 23 May 2024EweitzUse standard gene symbol
129844view02:52, 23 May 2024EweitzEconomize layout
129843view02:00, 23 May 2024EweitzFix MT end positioning
129842view01:59, 23 May 2024EweitzRefine transmembrane positioning
129841view01:58, 23 May 2024EweitzEconomize layout
129840view01:40, 23 May 2024EweitzUse standard gene symbol
129839view01:36, 23 May 2024EweitzFix interaction path, increase font
129838view01:34, 23 May 2024EweitzEconomize layout
129837view01:26, 23 May 2024EweitzEconomize layout
129836view01:07, 23 May 2024EweitzImprove readability: increase font size, narrow nodes, standardize case
129827view23:29, 22 May 2024EweitzPoint RTK and PI3K to gene families
117173view09:55, 18 May 2021EweitzModified title
106497view21:44, 4 September 2019KhanspersModified description
105803view22:51, 15 August 2019KhanspersModified description
105148view19:54, 11 July 2019AlexanderPicoFixed node labels
105051view23:46, 2 July 2019AlexanderPicoModified description
105050view23:45, 2 July 2019AlexanderPicoModified description
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
59187view18:52, 22 February 2013MaintBotUpdated Ensembl data source
47074view00:04, 15 March 2012KhanspersModified categories
45644view14:47, 26 October 2011CarlosBorrotoSpecify description
44788view16:12, 3 October 2011CarlosBorrotoPeriodical save, work in progress
44787view16:02, 3 October 2011CarlosBorrotoPeriodical save, work in progress
44725view19:34, 28 September 2011CarlosBorrotoAdd AGT, AGTR1 and AGTR2
44714view16:14, 26 September 2011CarlosBorrotoPeriodical save, work in progress
44713view16:04, 26 September 2011CarlosBorrotoPeriodical save, work in progress
44712view15:53, 26 September 2011CarlosBorrotoPeriodical save, work in progress
44711view15:43, 26 September 2011CarlosBorrotoPeriodical save, work in progress
44710view15:33, 26 September 2011CarlosBorrotoPeriodical save, work in progress
44709view15:22, 26 September 2011CarlosBorrotoPeriodical save, work in progress

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ABL1GeneProductENSG00000097007 (Ensembl)
AKTGeneProductENSG00000142208 (Ensembl)
APCGeneProductENSG00000134982 (Ensembl)
AURKBGeneProductENSG00000178999 (Ensembl)
CAMKGeneProductENSG00000152495 (Ensembl)
CDC42GeneProductENSG00000070831 (Ensembl)
CDK1GeneProductENSG00000170312 (Ensembl)
CFLGeneProductENSG00000165410 (Ensembl)
CLASPGeneProductENSG00000074054 (Ensembl)
CLIPGeneProductENSG00000130779 (Ensembl)
CRMP2GeneProductENSG00000092964 (Ensembl)
DIAPH1GeneProductENSG00000131504 (Ensembl)
DVL1GeneProductENSG00000107404 (Ensembl)
ERKGeneProductENSG00000133216 (Ensembl)
GNAQ GeneProductENSG00000156052 (Ensembl)
GSK3BGeneProductENSG00000082701 (Ensembl)
ICISGeneProduct
LIMKGeneProductENSG00000106683 (Ensembl)
LL5bGeneProductENSG00000144824 (Ensembl)
LPRGeneProductENSG00000132670 (Ensembl)
MAP1BGeneProductENSG00000131711 (Ensembl)
MAPKAPK2GeneProductENSG00000162889 (Ensembl)
MAPRE1GeneProductENSG00000101367 (Ensembl)
MAPTGeneProductENSG00000186868 (Ensembl)
MARK2GeneProductENSG00000072518 (Ensembl)
MARKGeneProductENSG00000116141 (Ensembl)
MCAKGeneProductENSG00000142945 (Ensembl)
NTRK1GeneProductNTRK1 (HGNC)
NTRK2GeneProductNTRK2 (HGNC)
NTRK3GeneProductNTRK3 (HGNC)
PAKGeneProductENSG00000149269 (Ensembl)
PAR1GeneProductENSG00000072518 (Ensembl)
PAR3GeneProduct2151 (Entrez Gene)
PAR6GeneProductENSG00000102981 (Ensembl)
PI3KGeneProductWP5472 (WikiPathways)
PIP3MetaboliteCHEBI:16618 (ChEBI)
PKCGeneProductENSG00000154229 (Ensembl)
PRKACAGeneProductENSG00000072062 (Ensembl)
PTENGeneProductENSG00000171862 (Ensembl)
RAC1GeneProductENSG00000136238 (Ensembl)
RHOGeneProductENSG00000163914 (Ensembl)
ROCKGeneProductENSG00000067900 (Ensembl)
RhoGEFGeneProduct
SPRED1GeneProductENSG00000166068 (Ensembl)
SRCGeneProductENSG00000197122 (Ensembl)
STAT3GeneProductENSG00000168610 (Ensembl)
STMN1GeneProductENSG00000117632 (Ensembl)
TAOKGeneProductENSG00000160551 (Ensembl)
TESKGeneProductENSG00000070759 (Ensembl)
TIAM1GeneProductENSG00000156299 (Ensembl)
TPPPGeneProductENSG00000171368 (Ensembl)
TRIOGeneProductENSG00000038382 (Ensembl)
WNTGeneProductENSG00000154342 (Ensembl)
XMAP215GeneProduct

Annotated Interactions

No annotated interactions

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