“DCTN6”的意思、由来-开放百科全书

In molecular biology, DCTN6 is that subunit of the dynactin protein complex that is encoded by the p27 gene. Dynactin is the essential component for microtubule-based cytoplasmic dynein motor activity in intracellular transport of a variety of cargoes and organelles.

Identification and structure

DCTN6 was first identified and cloned as a subunit of the "pointed-end complex" of dynactin through biochemical purification.^[1]

X-ray crystal structure revealed that dynactin p27 forms an unusual left handed β-helix (LβH) domain, and its phosphorylation site T186 is in C-terminal disordered segment.^[2]

Function

In intracellular transport

Dynactin p27 forms a hetero-dimer with the other dynactin pointed-end complex subunit p25/DCTN5 in 1:1 ratio, and it is essential for p25 stability since they are co-knockdown by p27 RNAi. However, both p27 and p25 are not required for 19S dynactin complex integrity verified by velocity sedimentation.^[3]^[4] p27/DCTN6 and other dynactin pointed-end complex subunits (Arp11/Actr10, p62/DCTN4, and p25/DCTN5) have been suggested to be involved in dynactin binding to specific intracellular cargoes.^[5] Co-depletion of dynactin p27 and p25 by p27 RNAi affects dynactin binding to endomembrane, and early and recycling endosome movements are impaired, suggesting that p27/p25 form a selective endomembrane cargo-targeting module.^[6]

In mitosis

In mitosis, unlike dynactin or dynein perturbation that causes mitotic spindle disarrangement and mitotic arrest, dynactin p27/p25 depletion does not affect mitotic spindle formation, pole focusing or dynein/dynactin targeting to kinetochores. However, dynactin p27/p25 are required for normal chromosome alignment, kinetochore-microtubule interaction, and proper timing of anaphase onset. Dynactin p27 C-terminal T186 residue is phosphorylated by cyclin-dependent kinase 1 (Cdk1) in mitosis and helps target polo-like kinase 1 (Plk1) to kinetochores during prometaphase. This activity facilitates phosphorylation of important downstream kinetochore targets (such as tension-sensing 3F3/2 phospho-epitope) of Plk1, which is important for recruitment of spindle assembly checkpoint proteins such as Mad1 and proper kinetochore-microtubule attachment.

References

1. ^{{cite journal|last=Eckley|first=DM|author2=Gill, SR |author3=Melkonian, KA |author4=Bingham, JB |author5=Goodson, HV |author6=Heuser, JE |author7= Schroer, TA |title=Analysis of dynactin subcomplexes reveals a novel actin-related protein associated with the arp1 minifilament pointed end.|journal=The Journal of Cell Biology|date=Oct 18, 1999|volume=147|issue=2|pages=307–20|pmid=10525537|doi=10.1083/jcb.147.2.307|pmc=2174220}}
2. ^{{cite journal|last=Yeh|first=TY|author2=Kowalska, AK |author3=Scipioni, BR |author4=Cheong, FK |author5=Zheng, M |author6=Derewenda, U |author7=Derewenda, ZS |author8= Schroer, TA |title=Dynactin helps target Polo-like kinase 1 to kinetochores via its left-handed beta-helical p27 subunit.|journal=The EMBO Journal|date=Apr 3, 2013|volume=32|issue=7|pages=1023–35|pmid=23455152|doi=10.1038/emboj.2013.30 |pmc=3616283}}
3. ^{{cite journal|last=Eckley|first=DM|author2=Gill, SR |author3=Melkonian, KA |author4=Bingham, JB |author5=Goodson, HV |author6=Heuser, JE |author7= Schroer, TA |title=Analysis of dynactin subcomplexes reveals a novel actin-related protein associated with the arp1 minifilament pointed end.|journal=The Journal of Cell Biology|date=Oct 18, 1999|volume=147|issue=2|pages=307–20|pmid=10525537|doi=10.1083/jcb.147.2.307|pmc=2174220}}
4. ^{{cite journal|last=Yeh|first=TY|author2=Quintyne, NJ |author3=Scipioni, BR |author4=Eckley, DM |author5= Schroer, TA |title=Dynactin's pointed-end complex is a cargo-targeting module.|journal=Molecular Biology of the Cell|date=October 2012|volume=23|issue=19|pages=3827–37|pmid=22918948|doi=10.1091/mbc.E12-07-0496 |pmc=3459859}}
5. ^{{cite journal|last=Schroer|first=TA|title=Dynactin.|journal=Annual Review of Cell and Developmental Biology|year=2004|volume=20|pages=759–79|pmid=15473859|doi=10.1146/annurev.cellbio.20.012103.094623}}
6. ^{{cite journal|last=Yeh|first=TY|author2=Quintyne, NJ |author3=Scipioni, BR |author4=Eckley, DM |author5= Schroer, TA |title=Dynactin's pointed-end complex is a cargo-targeting module.|journal=Molecular Biology of the Cell|date=October 2012|volume=23|issue=19|pages=3827–37|pmid=22918948|doi=10.1091/mbc.E12-07-0496 |pmc=3459859}}