The KIF3B/B/KAP3 tail domain specifically facilitates TRIM46 transport to the axon initial segment

Neurons rely on molecular motors to deliver proteins to precise locations. This study shows that kinesin-2 motors form heterogeneous assemblies with distin

Analysis of motor-based transport in primary cilia by dynamic mode decomposition of live-cell imaging data

Kinesin 3 motor proteins are increasingly recognized for their important roles in cilia. The mammalian kinesin 3 motor KIF13B moves bidirectionally in primary cilia and regulates ciliary content, but its relationship to the intraflagellar transport (IFT) machinery is unclear. Here, we combine quantitative live cell imaging with a new kymograph analysis based on dynamic mode decomposition (DMD) to separate mobile from immobile protein populations in primary cilia. This approach simplifies extraction of molecular velocities from kymographs and reveals that a KIF13B deletion mutant retaining only the motor domain and part of the forkhead-associated domain does not alter steady state IFT velocity or frequency. However, when retrograde dynein 2 function is inhibited by Ciliobrevin D, both anterograde and retrograde IFT velocities decrease in parental cells, as expected, but remain unchanged in KIF13B mutant cells. Structured illumination, confocal, and STED microscopy further show that KIF13B localizes to the ciliary membrane and concentrates at the periciliary membrane region and the centriolar subdistal appendages, below the distal appendage marker FBF1. Our improved kymograph approach provides new insight into KIF13B ciliary function and simplifies the quantitative analysis of ciliary protein transport. ### Competing Interest Statement The authors have declared no competing interest. Carlsberg Foundation, CF22-0670, CF23-1086 Novo Nordisk Foundation, https://ror.org/04txyc737, NNF18SA0032928, NNF22OC0080406

Kinase-gated coincidence detection controls kinesin-driven lysosome transport

Kinesin motors drive long-range intracellular transport through coordinated cargo recognition and conformational autoregulation, yet the mechanisms that selectively control cargo engagement remain unclear. Here, we identify a phosphorylation-dependent gate on kinesin-1 activity mediated by the carboxy-terminal domain (CTD) of kinesin light chain 2 (KLC2). The KLC2 CTD is constitutively phosphorylated on multiple serine residues, suppressing membrane association via its amphipathic helix. We identify the NIMA-related kinase NEK10 as a KLC2-selective regulator of kinesin-1, restraining motor activation, cargo engagement, and lysosome transport; conversely, loss of NEK10 increases membrane association and, together with low-affinity adaptor interactions, promotes lysosome motility. These findings reveal a phosphorylation-regulated protein-lipid coincidence-detection mechanism - a kinesin-kinase code - that integrates adaptor binding with membrane cues to control kinesin-1-mediated transport and provide a mechanistic basis for understanding paralogue and isoform diversity in the kinesin-1 family. ### Competing Interest Statement The authors have declared no competing interest. Biotechnology and Biological Sciences Research Council, BB/W005581/1, BB/Z517276/1 Lister Institute of Preventive Medicine, https://ror.org/03356n642

JCI Insight - KIF5A downregulation in spinal muscular atrophy links axonal regeneration defects with ALS