SPIN(DLY)-OFF: A tale of conformational change to control DYNEIN

Abstract

Barbosa et al. discuss work by Mussachio and colleagues (2022. J. Cell Biol.https://doi.org/10.1083/jcb.202206131) finding that conformational changes in the DYNEIN adaptor SPINDLY can precisely control DYNEIN activation at kinetochores.

Figure 1.

Conformational changes in SPINDLY control DYNEIN activation at kinetochores. (A) Schematic representation of native human SPINDLY according to the model by d’Amico et al. (7). Structural motifs in SPINDLY are highlighted (HBS1—heavy chain binding site 1; also referred to as CC2 box). Autoinhibited SPINDLY adopts a “closed” conformation that prevents its binding to DYNEIN-DYNACTIN. (B) During early mitosis, farnesylated SPINDLY localizes to kinetochores by binding to the RZZ complex and to a second receptor (“?”). Through this two-step mechanism, SPINDLY can interact with DYNEIN-DYNACTIN. As part of the fibrous corona, DYNEIN-DYNACTIN-SPINDLY assists in chromosome movement. Later in metaphase, the motor complex also contributes to corona disassembly by promoting RZZ removal from kinetochores.