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      Adapter Proteins for Opposing Motors Interact Simultaneously with Nuclear Pore Protein Nup358.

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          Abstract

          Nup358 is a protein subunit of the nuclear pore complex that recruits the opposing microtubule motors kinesin-1 and dynein [via the dynein adaptor Bicaudal D2 (BicD2)] to the nuclear envelope. This pathway is important for positioning of the nucleus during the early steps of mitotic spindle assembly and also essential for an important process in brain development. It is unknown whether dynein and kinesin-1 interact with Nup358 simultaneously or whether they compete. Here, we have reconstituted and characterized a minimal complex of kinesin-1 light chain 2 (KLC2) and Nup358. The proteins interact through a W-acidic motif in Nup358, which is highly conserved among vertebrates but absent in insects. While Nup358 and KLC2 form predominantly monomers, their interaction results in the formation of 2:2 complexes, and the W-acidic motif is required for the oligomerization. In active motor complexes, BicD2 and KLC2 each form dimers. Notably, we show that the dynein adaptor BicD2 and KLC2 interact simultaneously with Nup358, resulting in the formation of 2:2:2 complexes. Mutation of the W-acidic motif results in the formation of 1:1:1 complexes. On the basis of our data, we propose that Nup358 recruits simultaneously one kinesin-1 motor and one dynein motor via BicD2 to the nucleus. We hypothesize that the binding sites are close enough to promote direct interactions between these motor recognition domains, which may be important for the regulation of the motility of these opposing motors. Our data provide important insights into a nuclear positioning pathway that is crucial for brain development and faithful chromosome segregation.

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          Author and article information

          Journal
          Biochemistry
          Biochemistry
          American Chemical Society (ACS)
          1520-4995
          0006-2960
          December 17 2019
          : 58
          : 50
          Affiliations
          [1 ] Department of Chemistry , Binghamton University , P.O. Box 6000, Binghamton , New York 13902 , United States.
          Article
          NIHMS1589418
          10.1021/acs.biochem.9b00907
          7243271
          31756096
          612aed76-24e6-4197-9a93-baf3d231884e
          History

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