DCTN1

DCTN1

A gene on chromosome 2p13 that encodes dynactin-1 (the largest subunit of dynactin), a macromolecular complex that binds to both microtubules and cytoplasmic dynein and effect an array of motor activities, including ER-to-Golgi transport, centripetal movement of lysosomes and endosomes, spindle formation, chromosome movement, nuclear positioning and axonogenesis.
 
Molecular pathology
DCTN1 mutations cause distal hereditary motor neuronopathy type VIIB (HMN7B).
References in periodicals archive ?
Interestingly, amongst the seven genes that have been identified to cause the disease, most have housekeeping functions, including small heat shock proteins (sHSP) (dHMN-II); glycyl tRNA synthetase (GARS) (dHMN-V); Berardinelli-Seip congenital lipodystrophy (BSCL2) (dHMN-V); immunoglobulin [micro]-binding protein-2 (IGHMBP2) (dHMN-VI); dynactin (DCTN1) (dHMN-VII); and senataxin (SETX) (dHMN) with pyramidal tract signs.
Abbreviations BSCL2: Berardinelli-Seip congenital lipodystrophy CMT2D: Charcot-Marie-Tooth 2D DCTN1: Dynactin subunit 1 dHMN: Distal hereditary motor neuropathies dSMA-V: Distal spinal muscular atrophy type V dSMA-Va: Distal spinal muscular atrophy type Va EMG: Electromyography ETC: Mitochondrial respiratory chain enzyme analysis GARS: Glycyl tRNA synthetase IGHMBP2: Immunoglobulin [mu]-binding protein-2 L: Leucine R: Arginine SETX: Senataxin sHSP: Small heat shock proteins SMA: Spinal muscular atrophy RSV: Respiratory syncytial virus VUS: Variant of unknown significance WES: Whole exome sequencing.
Among these, one of the striking observations is the differential expression of numerous ALS-linked genes (i.e., ANG, DCTN1, SQSTM1, and TBK1) involved in autophagy, a highly conserved and tightly regulated cellular self-degradative process whose alteration leads to an impaired clearance of toxic protein aggregates and/or of damaged mitochondria that represent some of the best characterized hallmarks of both SALS and FALS [61].
Abbreviations SOD1: Superoxide dismutase 1 ALS2: Alsin SETX: Senataxin SPG11: Spastic paraplegia 11 FUS: Fused in sarcoma RNA binding protein VAMP: Vesicle-associated membrane protein VAPB: Associated protein B and C ANG: Angiogenin TARDBP: TAR DNA-binding protein FIG4: FIG4 phosphoinositide 5-phosphatase OPTN: Optineurin ATXN2: Ataxin-2 C9ORF72: Chromosome 9 open reading frame 72 VEGF: Vascular endothelial growth factor IFN-[gamma]: Interferon gamma TNF-[alpha]: Tumor necrosis factor ILs: Interleukins IL-1[beta]: Interleukin 1 beta UBC: Ubiquitin C TBK1: TANK-binding kinase 1 SQSTM1: Sequestosome 1 DCTN1: Dynactin subunit 1 IMPAS-1: Histocompatibility minor 13.
We have also observed the downregulation of many genes involved in mitochondrial transport such as the family of dynactins (DCTN1, 2, 3, 5, and 6), dyneins (DYNC1H1, DYNC1I1, and DYNC1LI1), kinesins (KIF1B and KIF5C), and Miro (data not shown).
During the study, the researchers found that Perry syndrome patients have mutations in a subunit of the dynactin complex (DCTN1; p150glued), which is essential to the movement of molecular "cargo" inside brain cells, or neurons.
Upon studying the eight families with Perry syndrome, the Mayo-led team found that each family had one of five novel mutations in the DCTN1 gene, whose protein produces a large subunit of the dynactin complex known as p150glued.