Kinesin-13s are microtubule (MT) depolymerases different from most other kinesins that move along MTs. Like other kinesins, they have a motor or head domain (HD) containing a tubulin and an ATP binding site. Interestingly, kinesin-13s have an additional binding site (Kin-Tub-2) on the opposite side of the HD that contains several family conserved positively charged residues. The role of this site in kinesin-13 function is not clear. To address this issue, we investigated the in-vitro and in-vivo effects of mutating Kin-Tub-2 family conserved residues on the Drosophila melanogaster kinesin-13, KLP10A. We show that the Kin-Tub-2 site enhances tubulin cross-linking and MT bundling properties of KLP10A in-vitro. Disruption of the Kin-Tub-2 site, despite not having a deleterious effect on MT depolymerization, results in abnormal mitotic spindles and lagging chromosomes during mitosis in Drosophila S2 cells. The results suggest that the additional Kin-Tub-2 tubulin biding site plays a direct MT attachment role in-vivo.

Background: Coronavirus disease 2019 (COVID-19) has affected millions of people, and several chronic medical conditions appear to increase the risk of severe COVID-19. However, our understanding of COVID-19 outcomes in patients with chronic kidney disease (CKD) remains limited. Methods: This was a retrospective cohort study of patients with and without CKD consecutively admitted with COVID-19 to three affiliated hospitals in New York City. Pre-COVID-19 CKD diagnoses were identified by billing codes and verified by manual chart review. In-hospital mortality was compared between patients with and without underlying CKD. Logistic regression was used to adjust this analysis for confounders and to identify patient characteristics associated with mortality. Results: We identified 280 patients with CKD, and 4098 patients without CKD hospitalized with COVID-19. The median age of CKD group was 75 (65-84) years, and age of non-CKD group 62 (48-75) years. Baseline (pre-COVID-19) serum creatinine in patients with CKD was 1.5 (1.2-2.2) mg/dL. In-hospital mortality was 30% in patients with CKD vs. 19.9% in patients without CKD (p<0.001). The risk of in-hospital death in patients with CKD remained significantly higher after adjustment for comorbidities (hypertension, diabetes mellitus, asthma, and chronic obstructive pulmonary disease), adjusted OR 1.4 [1.1-1.9]. When stratified by age, elderly patients with CKD (above age 70) had higher mortality than their age-matched control patients without CKD. In patients with CKD, factors associated with in-hospital mortality were age (adjusted OR 1.09 [1.06-1.12]), baseline and admission serum phosphorus (adjusted ORs 1.5 [1.03-2.1] and 1.4 [1.1-1.7]), serum creatinine on admission >0.3 mg/dL above the baseline (adjusted OR 2.6 [1.2-5.4]), and diagnosis of acute on chronic kidney injury during hospitalization (adjusted OR 4.6 [2.3-8.9]). Conclusions: CKD is an independent risk factor for COVID-19 associated in-hospital mortality in elderly patients. Acute on chronic kidney injury increases odds of in-hospital mortality in CKD patients hospitalized with COVID-19.