HighlightsTransport between endocytic organelles involves microtubule and actin based molecular motors.Both cytoskeletal systems contribute to membrane deformation and scission.Transport of endosomes to and from the cell cortex requires transfer between actin and microtubules.
Cytoplasmic dynein-driven movement of chromosomes during prophase I of meiosis is essential for synapsis and genetic exchange. Dynein connects to chromosome telomeres via KASH5 and SUN1/2, which span the outer and inner nuclear envelopes, respectively. Here, we show that KASH5 promotes dynein motility in vitro, and cytosolic KASH5 inhibits dynein’s interphase functions. KASH5 interacts with either dynein light intermediate chain (DYNC1LI1 or DYNC1LI2) via a conserved linker-helix in the LIC C-terminal, and this region is also needed for dynein’s recruitment to other cellular membranes. KASH5’s N-terminal EF-hands are essential, as the interaction with dynein is disrupted by mutation of key calcium-binding residues, although it is not regulated by cellular calcium levels. Dynein can be recruited to KASH5 at the nuclear envelope independently of dynactin, while LIS1 is essential for dynactin incorporation into the KASH5-dynein complex. Altogether, we show that the trans-membrane protein KASH5 is an activating adaptor for dynein, and shed light on the hierarchy of assembly of KASH5-dynein-dynactin complexes.
Cytoplasmic dynein-driven movement of chromosomes during prophase I of mammalian meiosis is essential for synapsis and genetic exchange. Dynein connects to chromosome telomeres via KASH5 and SUN1 or SUN2, which together span the nuclear envelope. Here, we show that KASH5 promotes dynein motility in vitro, and cytosolic KASH5 inhibits dynein’s interphase functions. KASH5 interacts with a dynein light intermediate chain (DYNC1LI1 or DYNC1LI2) via a conserved helix in the LIC C-terminal, and this region is also needed for dynein’s recruitment to other cellular membranes. KASH5’s N-terminal EF-hands are essential as the interaction with dynein is disrupted by mutation of key calcium-binding residues, although it is not regulated by cellular calcium levels. Dynein can be recruited to KASH5 at the nuclear envelope independently of dynactin, while LIS1 is essential for dynactin incorporation into the KASH5–dynein complex. Altogether, we show that the transmembrane protein KASH5 is an activating adaptor for dynein and shed light on the hierarchy of assembly of KASH5–dynein–dynactin complexes.
From the Archives: minutes of meetings 50 years ago, written by the then Meetings Secretary, EJ Denton Features 22 Numberism: exploring science through art 26 Why are the problems associated with the lack of international standards for Ca 2+ /Mg 2+ buffers still being ignored? 30 Breath of the Sith: a case study on respiratory failure in a galaxy far, far away 34 The science of laughter Membership 38 Oh the places you'll go: my postdoc in the USA 40 My post-college year in the UK, 1949-50 42 Memories of a postdoctoral fellowship with Otto Hutter
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