Conference on retroviruses and opportunistic infections (virtual): March 6-10, 2021.

The Conference on Retroviruses and Opportunistic Infections (CROI) for 2021 was, as with so many other conferences in the past 12 months, held online. CROI provided a forum for basic scientists and clinical researchers to bring together and discuss their work on human retroviruses and associated diseases, with HIV and SARS-CoV-2 being the two viruses most covered this year. Below are some examples of the work presented at the conference, highlighting both the innovative approaches to understanding and treating viral infections but also the breadth of topics covered.

Opposing kinesin complexes queue at plus tips to ensure microtubule catastrophe at cell ends.

In fission yeast, the lengths of interphase microtubule (iMT) arrays are adapted to cell length to maintain cell polarity and to help centre the nucleus and cell division ring. Here, we show that length regulation of iMTs is dictated by spatially regulated competition between MT-stabilising Tea2/Tip1/Mal3 (Kinesin-7) and MT-destabilising Klp5/Klp6/Mcp1 (Kinesin-8) complexes at iMT plus ends. During MT growth, the Tea2/Tip1/Mal3 complex remains bound to the plus ends of iMT bundles, thereby restricting access to the plus ends by Klp5/Klp6/Mcp1, which accumulate behind it. At cell ends, Klp5/Klp6/Mcp1 invades the space occupied by the Tea2/Tip1/Tea1 kinesin complex triggering its displacement from iMT plus ends and MT catastrophe. These data show that in vivo, whilst an iMT length-dependent model for catastrophe factor accumulation has validity, length control of iMTs is an emergent property reflecting spatially regulated competition between distinct kinesin complexes at the MT plus tip.

Identification of a Sgo2-Dependent but Mad2-Independent Pathway Controlling Anaphase Onset in Fission Yeast.

The onset of anaphase is triggered by activation of the anaphase-promoting complex/cyclosome (APC/C) following silencing of the spindle assembly checkpoint (SAC). APC/C triggers ubiquitination of Securin and Cyclin B, which leads to loss of sister chromatid cohesion and inactivation of Cyclin B/Cdk1, respectively. This promotes relocalization of Aurora B kinase and other components of the chromosome passenger complex (CPC) from centromeres to the spindle midzone. In fission yeast, this is mediated by Clp1 phosphatase-dependent interaction of CPC with Klp9/MKLP2 (kinesin-6). When this interaction is disrupted, kinetochores bi-orient normally, but APC/C activation is delayed via a mechanism that requires Sgo2 and some (Bub1, Mph1/Mps1, and Mad3), but not all (Mad1 and Mad2), components of the SAC and the first, but not second, lysine, glutamic acid, glutamine (KEN) box in Mad3. These data indicate that interaction of CPC with Klp9 terminates a Sgo2-dependent, but Mad2-independent, APC/C-inhibitory pathway that is distinct from the canonical SAC.

Role and regulation of kinesin-8 motors through the cell cycle.

Members of the kinesin-8 motor family play a central role in controlling microtubule length throughout the eukaryotic cell cycle. Inactivation of kinesin-8 causes defects in cell polarity during interphase and astral and mitotic spindle length, metaphase chromosome alignment, timing of anaphase onset and accuracy of chromosome segregation. Although the biophysical mechanism by which kinesin-8 molecules influence microtubule dynamics has been studied extensively in a variety of species, a consensus view has yet to emerge. One reason for this might be that some members of the kinesin-8 family can associate to other microtubule-associated proteins, cell cycle regulatory proteins and other kinesin family members. In this review we consider how cell cycle specific modification and its association to other regulatory proteins may modulate the function of kinesin-8 to enable it to function as a master regulator of microtubule dynamics.