Dynein alone?

I evaluated the following article for F1000:

Dynein light chain 1 and a spindle-associated adaptor promote dynein asymmetry and spindle orientation.
AK Dunsch, D Hammond, J Lloyd, L Schermelleh, U Gruneberg and FA Barr J Cell Biol. 2012 Sep 17; 198(6): 1039-54
PMID: 22965910 DOI: 10.1083/jcb.201202112

The thing that fascinates me the most about this is the possibility that dynein containing light chain-1 acts without dynactin…..hence the crap title for the post.

This paper is highly intriguing from a dynein motor perspective as it strongly suggests that, in mitosis, the binding of dynein light chain 1 (DYNLL1) and the major dynein regulator dynactin are mutually exclusive. The work details very clearly how the adaptor proteins CHICA and HMMR target dynein to the mitotic spindle. This serves to control spindle positioning in cells, at least in part through promoting dynein asymmetry. It will be fascinating to determine whether DYNLL1 and dynactin can bind to dynein at the same time in interphase cells; this would of course have major implications for those studying dynein and dynactin function.


5 thoughts on “Dynein alone?

  1. See also:
    1. Stuchell-Brereton, M. D. et al. Functional interaction between dynein light chain and intermediate chain is required for mitotic spindle positioning. Mol Biol Cell (2011).doi:10.1091/mbc.E11-01-0075

    1. McKenney, R. J., Weil, S. J., Scherer, J. & Vallee, R. B. Mutually Exclusive Cytoplasmic Dynein Regulation by NudE-Lis1 and Dynactin. J Biol Chem 286, 39615–39622 (2011).

    • Both very appropriate refs to highlight. Thanks dynein dude. Great handle btw. Vale lab I assume…. 😉
      Will comment more when I have some time.

      • Hi David,

        I think your conclusions about the mutual exclusivity of LC8 and dynactin may be premature. In fact the Stuchell-Brereton paper comes to the directly opposite conclusion, that LC8 is actually necessary for dynein-dynactin interaction. The only hard data presented in the Dunsch paper is the lack of dynactin in their LC8 IP’s. But this is hardly surprising as one almost never sees dynactin in IP’s of dynein (interestingly, see Splinter et al. MBoC in press). Their hypothesis about an LC8 gradient is interesting, but speculative at best. The most likely scenario is that LC8 binding is required to stabilize a dimer of CHICA, which in turn is necessary for the downstream functions of this protein. See the great work fromt the Barbar lab about LC8 being a dimerization factor, apparently in many contexts even outside of the dynein pathway.

        Dynein dude

      • These are all very good points, I think that the point that others see Lc8 as being required for the dynein interaction is interesting but if I am correct, this was in S. cerevisiae not mammals. Things are clearly different between species. Second, I can address your point about dynein and dynactin interactions more directly. We, like others, struggle to coIP these two complexes but in our own proteomics work (after tagging light intermediate chains) we can indeed pull down the entire dynactin complex as well as all other components of dynein. We haven’t yet published these data as we are struggling to validate by immunoblotting, this entirely goes along with the inability to coIP dynein with dynactin of course!
        Undoubtedly there is much more to come from this story.

  2. The proteomics work sounds very interesting, looking forward to reading the paper! The LIC’s are mysterious subunits.

    Also looking forward to more blog posts (about dynein hopefully!)

    Dynein dude

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