Dynactin has two antagonistic regulatory domains and exerts opposing effects on dynein motility

PloS One
Takuya KobayashiYoko Y Toyoshima

Abstract

Dynactin is a dynein-regulating protein that increases the processivity of dynein movement on microtubules. Recent studies have shown that a tripartite complex of dynein-dynactin-Bicaudal D2 is essential for highly processive movement. To elucidate the regulation of dynein motility by dynactin, we focused on two isoforms (A and B) of dynactin 1 (DCTN1), the largest subunit of dynactin that contains both microtubule- and dynein-binding domains. The only difference between the primary structures of the two isoforms is that DCTN1B lacks the K-rich domain, a cluster of basic residues. We measured dynein motility by single molecule observation of recombinant dynein and dynactin. Whereas the tripartite complex containing DCTN1A exhibited highly processive movement, the complex containing DCTN1B dissociated from microtubules with no apparent processive movement. This inhibitory effect of DCTN1B was caused by reductions of the microtubule-binding affinities of both dynein and dynactin, which was attributed to the coiled-coil 1 domain of DCTN1. In DCTN1A, the K-rich domain antagonized these inhibitory effects. Therefore, dynactin has two antagonistic domains and promotes or suppresses dynein motility to accomplish correct localization a...Continue Reading

References

May 1, 1975·Proceedings of the National Academy of Sciences of the United States of America·M D WeingartenM W Kirschner
Dec 1, 1995·The Journal of Biological Chemistry·S B Karki, Erika L F Holzbaur
Nov 1, 1994·Current Biology : CB·V Allan
Feb 28, 1995·Proceedings of the National Academy of Sciences of the United States of America·C M Waterman-StorerErika L F Holzbaur
Nov 7, 1998·Biochimica Et Biophysica Acta·Mariko Tokito, Erika L F Holzbaur
Jan 6, 2000·Nature Cell Biology·S J King, T A Schroer
Jan 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·Y Okada, N Hirokawa
Sep 11, 2002·The Journal of Biological Chemistry·Songlin LiMing Luo
Jan 29, 2003·The Journal of Cell Biology·Sean W DeaconVladimir I Gelfand
Apr 11, 2003·Molecular Biology of the Cell·Lee A LigonErika L F Holzbaur
Oct 12, 2004·Annual Review of Cell and Developmental Biology·T A Schroer
Apr 14, 2005·The Journal of Biological Chemistry·I R GibbonsAndrew P Carter
Oct 22, 2005·Annals of Neurology·Christoph MünchAlbert C Ludolph
Dec 14, 2005·Biochemical and Biophysical Research Communications·Takuya KobayashiYoko Y Toyoshima
Feb 14, 2006·Nature Cell Biology·Tara L Culver-HanlonStephen J King
Sep 11, 2007·Nature Structural & Molecular Biology·Anke WeisbrichMichel O Steinmetz
May 20, 2008·Developmental Biology·Karsten H Siller, Chris Q Doe
Sep 25, 2008·The Journal of Biological Chemistry·Ram DixitErika L F Holzbaur
Jan 13, 2009·Nature Genetics·Matthew J FarrerZbigniew K Wszolek
Feb 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Cynthia K ShrumMollie K Meffert
Mar 19, 2009·Proceedings of the National Academy of Sciences of the United States of America·Julia R KardonRonald D Vale
Nov 26, 2009·Nature Reviews. Molecular Cell Biology·Julia R Kardon, Ronald D Vale
Nov 26, 2009·Biopolymers·Soccorsa PensatoAlessandra Romanelli
May 4, 2010·Movement Disorders : Official Journal of the Movement Disorder Society·Victoria NewswayHuw R Morris
May 24, 2011·Nature Structural & Molecular Biology·Takahide KonGenji Kurisu
Mar 27, 2012·Current Biology : CB·Adam G HendricksErika L F Holzbaur
Jul 23, 2013·PLoS Biology·Jacob E LazarusErika L F Holzbaur
Jul 6, 2014·The EMBO Journal·Max A SchlagerAndrew P Carter
Jul 19, 2014·Science·Richard J McKenneyRonald D Vale
Oct 1, 2014·Nature Cell Biology·Takayuki TorisawaKen'ya Furuta
Nov 25, 2014·Nature Cell Biology·Suvranta K TripathySteven P Gross
Mar 31, 2015·Science·Linas UrnaviciusAndrew P Carter

Citations

Aug 3, 2018·Journal of Virology·Stephanie K CarnesChristopher Aiken
Apr 18, 2018·Nature Reviews. Molecular Cell Biology·Samara L Reck-PetersonAndrew P Carter
Apr 3, 2020·Molecular Biology of the Cell·Kei SaitoYoko Y Toyoshima
Feb 22, 2020·Frontiers in Cell and Developmental Biology·Takayuki Torisawa, Akatsuki Kimura
May 1, 2018·Current Biology : CB·Paulomi SanghaviRoop Mallik

Methods Mentioned

BETA
PCR
electrophoresis
pull-down

Related Concepts

dynactin subunit 1
Dynein Intermediate Chains
Microtubules
Protein Isoforms
HEK293 Cells
Cell Motility
Dynein ATPase
Recombinant Proteins
Binding Protein
Antagonists

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Alzheimer's Disease: MS4A

Variants within the membrane-spanning 4-domains subfamily A (MS4A) gene cluster have recently been implicated in Alzheimer's disease in genome-wide association studies. Here is the latest research on Alzheimer's disease and MS4A.

Pediculosis pubis

Pediculosis pubis is a disease caused by a parasitic insect known as Pthirus pubis, which infests human pubic hair, as well as other areas with hair including eye lashes. Here is the latest research.

Rh Isoimmunization

Rh isoimmunization is a potentially preventable condition that occasionally is associated with significant perinatal morbidity or mortality. Discover the latest research on Rh Isoimmunization here.

Genetic Screens in iPSC-derived Brain Cells

Genetic screening is a critical tool that can be employed to define and understand gene function and interaction. This feed focuses on genetic screens conducted using induced pluripotent stem cell (iPSC)-derived brain cells. It also follows CRISPR-Cas9 approaches to generating genetic mutants as a means of understanding the effect of genetics on phenotype.

Enzyme Evolution

This feed focuses on molecular models of enzyme evolution and new approaches (such as adaptive laboratory evolution) to metabolic engineering of microorganisms. Here is the latest research.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Pharmacology of Proteinopathies

This feed focuses on the pharmacology of proteinopathies - diseases in which proteins abnormally aggregate (i.e. Alzheimer’s, Parkinson’s, etc.). Discover the latest research in this field with this feed.

Alignment-free Sequence Analysis Tools

Alignment-free sequence analyses have been applied to problems ranging from whole-genome phylogeny to the classification of protein families, identification of horizontally transferred genes, and detection of recombined sequences. Here is the latest research.