Microtubule cytoskeleton regulation (WP2038)

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 (STMN), 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 [https://assays.cancer.gov/available_assays?wp_id=WP2038 CPTAC Assay Portal]
last edited

Authors

CarlosBorroto, Khanspers, MaintBot, Zari, Lindarieswijk, Mkutmon, AlexanderPico, and Eweitz

Cited In

Organism

Homo sapiens

Communities

Annotations

Pathway Ontology: cell-extracellular matrix signaling pathway

Participants

Label Type Compact Identifier
Rho GeneProduct ensembl:ENSG00000163914
TAU GeneProduct ensembl:ENSG00000186868
LL5b GeneProduct ensembl:ENSG00000144824
TPPP GeneProduct ensembl:ENSG00000171368
LIMK GeneProduct ensembl:ENSG00000106683
TESK GeneProduct ensembl:ENSG00000070759
MAPKAPK GeneProduct ensembl:ENSG00000162889
DVL GeneProduct ensembl:ENSG00000107404
PKC GeneProduct ensembl:ENSG00000154229
PAR6 GeneProduct ensembl:ENSG00000102981
TAOK GeneProduct ensembl:ENSG00000160551
SPRED1 GeneProduct ensembl:ENSG00000166068
ROCK GeneProduct ensembl:ENSG00000067900
RAC1 GeneProduct ensembl:ENSG00000136238
MARK GeneProduct ensembl:ENSG00000116141
CFL GeneProduct ensembl:ENSG00000165410
GSK3B GeneProduct ensembl:ENSG00000082701
MARK2 GeneProduct ensembl:ENSG00000072518
PAR3 GeneProduct ncbigene:2151
PAR1 GeneProduct ensembl:ENSG00000072518
PTEN GeneProduct ensembl:ENSG00000171862
AKT GeneProduct ensembl:ENSG00000142208
ERK GeneProduct ensembl:ENSG00000133216
CDC42 GeneProduct ensembl:ENSG00000070831
PIK3 GeneProduct ensembl:ENSG00000121879
GNAQ GeneProduct ensembl:ENSG00000156052
WNT GeneProduct ensembl:ENSG00000154342
LPR GeneProduct ensembl:ENSG00000132670
STAT3 GeneProduct ensembl:ENSG00000168610
STMN GeneProduct ensembl:ENSG00000117632
PAK GeneProduct ensembl:ENSG00000149269
PRKACA GeneProduct ensembl:ENSG00000072062
AURKB GeneProduct ensembl:ENSG00000178999
CAMK GeneProduct ensembl:ENSG00000152495
CDK1 GeneProduct ensembl:ENSG00000170312
MCAK GeneProduct ensembl:ENSG00000142945
XMAP215 GeneProduct None
ICIS GeneProduct None
RhoGEF GeneProduct None
c-ABL GeneProduct ensembl:ENSG00000097007
TRIO GeneProduct ensembl:ENSG00000038382
TIAM1 GeneProduct ensembl:ENSG00000156299
SRC GeneProduct ensembl:ENSG00000197122
CLASP GeneProduct ensembl:ENSG00000074054
CLIP GeneProduct ensembl:ENSG00000130779
MAP1B GeneProduct ensembl:ENSG00000131711
CRMP2 GeneProduct ensembl:ENSG00000092964
EB1 GeneProduct ensembl:ENSG00000101367
APC GeneProduct ensembl:ENSG00000134982
mDIA GeneProduct ncbigene:1729
mDIA GeneProduct ncbigene:1729
EB1 GeneProduct ensembl:ENSG00000101367
CLIP GeneProduct ensembl:ENSG00000130779
CLIP GeneProduct ensembl:ENSG00000130779
CLIP GeneProduct ensembl:ENSG00000130779
CLASP GeneProduct ensembl:ENSG00000074054
EB1 GeneProduct ensembl:ENSG00000101367
APC GeneProduct ensembl:ENSG00000134982
RAC1 GeneProduct ensembl:ENSG00000136238
Rho GeneProduct ensembl:ENSG00000163914
mDIA1 GeneProduct ncbigene:1729
GNAQ GeneProduct ensembl:ENSG00000156052
Rho GeneProduct ensembl:ENSG00000163914
Rho GeneProduct ensembl:ENSG00000163914
MAP1B GeneProduct ensembl:ENSG00000131711
ERK GeneProduct ensembl:ENSG00000133216

References

  1. Etienne-Manneville S. From signaling pathways to microtubule dynamics: the key players. Curr Opin Cell Biol. 2010 Feb;22(1):104–11. PubMed Europe PMC Scholia
  2. Anitei M, Hoflack B. Bridging membrane and cytoskeleton dynamics in the secretory and endocytic pathways. Nat Cell Biol. 2011 Dec 22;14(1):11–9. PubMed Europe PMC Scholia