| Structural highlights
Function
[DYL1_HUMAN] Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in changing or maintaining the spatial distribution of cytoskeletal structures.[1] [2] [3] [4] Binds and inhibits the catalytic activity of neuronal nitric oxide synthase.[5] [6] [7] [8] Promotes transactivation functions of ESR1 and plays a role in the nuclear localization of ESR1.[9] [10] [11] [12] Regulates apoptotic activities of BCL2L11 by sequestering it to microtubules. Upon apoptotic stimuli the BCL2L11-DYNLL1 complex dissociates from cytoplasmic dynein and translocates to mitochondria and sequesters BCL2 thus neutralizing its antiapoptotic activity.[13] [14] [15] [16]
Publication Abstract from PubMed
The close association of myelinated axons and their myelin sheaths involves numerous intercellular molecular interactions. For example, myelin-associated glycoprotein (MAG) mediates myelin-to-axon adhesion and signalling via molecules on the axonal surface. However, knowledge about intracellular binding partners of myelin proteins, including MAG, has remained limited. The two splice isoforms of MAG, S- and L-MAG, display distinct cytoplasmic domains and spatiotemporal expression profiles. We used yeast 2-hybrid screening to identify interaction partners of L-MAG and found the dynein light chain DYNLL1 (also termed DLC8). DYNLL1 homodimers are known to facilitate dimerization of target proteins. L-MAG and DYNLL1 associate with high affinity, as confirmed with recombinant proteins in vitro. Structural analyses of the purified complex indicate that the DYNLL1-binding segment is localized close to the L-MAG C terminus, next to the Fyn kinase Tyr phosphorylation site. The crystal structure of the complex between DYNLL1 and its binding segment on L-MAG shows 2:2 binding in a parallel arrangement, indicating a heterotetrameric complex. The homology between L-MAG and previously characterized DYNLL1-ligands is limited, and some details of binding-site interactions are unique for L-MAG. The structure of the complex between the entire L-MAG cytoplasmic domain and DYNLL1, as well as that of the the extracellular domain of MAG, were modeled based on small-angle X-ray scattering data, allowing structural insights into L-MAG interactions on both membrane surfaces. Our data imply that DYNLL1 dimerizes L-MAG, but not S-MAG, through the formation of a specific 2:2 heterotetramer. This arrangement is likely to affect, in an isoform-specific manner, the functions of MAG in adhesion and myelin-to-axon signalling. This article is protected by copyright. All rights reserved.
High-affinity heterotetramer formation between the large myelin-associated glycoprotein and the dynein light chain DYNLL1.,Myllykoski M, Eichel MA, Jung RB, Kelm S, Werner HB, Kursula P J Neurochem. 2018 Sep 27. doi: 10.1111/jnc.14598. PMID:30261098[17]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Puthalakath H, Huang DC, O'Reilly LA, King SM, Strasser A. The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Mol Cell. 1999 Mar;3(3):287-96. PMID:10198631
- ↑ Vadlamudi RK, Bagheri-Yarmand R, Yang Z, Balasenthil S, Nguyen D, Sahin AA, den Hollander P, Kumar R. Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes. Cancer Cell. 2004 Jun;5(6):575-85. PMID:15193260 doi:10.1016/j.ccr.2004.05.022
- ↑ Rayala SK, den Hollander P, Balasenthil S, Yang Z, Broaddus RR, Kumar R. Functional regulation of oestrogen receptor pathway by the dynein light chain 1. EMBO Rep. 2005 Jun;6(6):538-44. PMID:15891768 doi:10.1038/sj.embor.7400417
- ↑ Rayala SK, den Hollander P, Manavathi B, Talukder AH, Song C, Peng S, Barnekow A, Kremerskothen J, Kumar R. Essential role of KIBRA in co-activator function of dynein light chain 1 in mammalian cells. J Biol Chem. 2006 Jul 14;281(28):19092-9. Epub 2006 May 9. PMID:16684779 doi:10.1074/jbc.M600021200
- ↑ Puthalakath H, Huang DC, O'Reilly LA, King SM, Strasser A. The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Mol Cell. 1999 Mar;3(3):287-96. PMID:10198631
- ↑ Vadlamudi RK, Bagheri-Yarmand R, Yang Z, Balasenthil S, Nguyen D, Sahin AA, den Hollander P, Kumar R. Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes. Cancer Cell. 2004 Jun;5(6):575-85. PMID:15193260 doi:10.1016/j.ccr.2004.05.022
- ↑ Rayala SK, den Hollander P, Balasenthil S, Yang Z, Broaddus RR, Kumar R. Functional regulation of oestrogen receptor pathway by the dynein light chain 1. EMBO Rep. 2005 Jun;6(6):538-44. PMID:15891768 doi:10.1038/sj.embor.7400417
- ↑ Rayala SK, den Hollander P, Manavathi B, Talukder AH, Song C, Peng S, Barnekow A, Kremerskothen J, Kumar R. Essential role of KIBRA in co-activator function of dynein light chain 1 in mammalian cells. J Biol Chem. 2006 Jul 14;281(28):19092-9. Epub 2006 May 9. PMID:16684779 doi:10.1074/jbc.M600021200
- ↑ Puthalakath H, Huang DC, O'Reilly LA, King SM, Strasser A. The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Mol Cell. 1999 Mar;3(3):287-96. PMID:10198631
- ↑ Vadlamudi RK, Bagheri-Yarmand R, Yang Z, Balasenthil S, Nguyen D, Sahin AA, den Hollander P, Kumar R. Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes. Cancer Cell. 2004 Jun;5(6):575-85. PMID:15193260 doi:10.1016/j.ccr.2004.05.022
- ↑ Rayala SK, den Hollander P, Balasenthil S, Yang Z, Broaddus RR, Kumar R. Functional regulation of oestrogen receptor pathway by the dynein light chain 1. EMBO Rep. 2005 Jun;6(6):538-44. PMID:15891768 doi:10.1038/sj.embor.7400417
- ↑ Rayala SK, den Hollander P, Manavathi B, Talukder AH, Song C, Peng S, Barnekow A, Kremerskothen J, Kumar R. Essential role of KIBRA in co-activator function of dynein light chain 1 in mammalian cells. J Biol Chem. 2006 Jul 14;281(28):19092-9. Epub 2006 May 9. PMID:16684779 doi:10.1074/jbc.M600021200
- ↑ Puthalakath H, Huang DC, O'Reilly LA, King SM, Strasser A. The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Mol Cell. 1999 Mar;3(3):287-96. PMID:10198631
- ↑ Vadlamudi RK, Bagheri-Yarmand R, Yang Z, Balasenthil S, Nguyen D, Sahin AA, den Hollander P, Kumar R. Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes. Cancer Cell. 2004 Jun;5(6):575-85. PMID:15193260 doi:10.1016/j.ccr.2004.05.022
- ↑ Rayala SK, den Hollander P, Balasenthil S, Yang Z, Broaddus RR, Kumar R. Functional regulation of oestrogen receptor pathway by the dynein light chain 1. EMBO Rep. 2005 Jun;6(6):538-44. PMID:15891768 doi:10.1038/sj.embor.7400417
- ↑ Rayala SK, den Hollander P, Manavathi B, Talukder AH, Song C, Peng S, Barnekow A, Kremerskothen J, Kumar R. Essential role of KIBRA in co-activator function of dynein light chain 1 in mammalian cells. J Biol Chem. 2006 Jul 14;281(28):19092-9. Epub 2006 May 9. PMID:16684779 doi:10.1074/jbc.M600021200
- ↑ Myllykoski M, Eichel MA, Jung RB, Kelm S, Werner HB, Kursula P. High-affinity heterotetramer formation between the large myelin-associated glycoprotein and the dynein light chain DYNLL1. J Neurochem. 2018 Sep 27. doi: 10.1111/jnc.14598. PMID:30261098 doi:http://dx.doi.org/10.1111/jnc.14598
|
