Retrograde axonal transport requires an intricate interaction between the dynein motor and its cargo. What mediates this interaction is largely unknown. Using forward genetics and a novel in vivo imaging approach, we identified JNK-interacting protein 3 (Jip3) as a direct mediator of dynein-based retrograde transport of activated (phosphorylated) c-Jun N-terminal Kinase (JNK) and lysosomes. Zeb...

The murine JNK-interacting protein 3 (JIP3) protein (also known as JSAP1) is expressed exclusively in neurons and has been identified as a scaffold protein for the c-Jun NH2-terminal kinase (JNK) signaling pathway and as an adapter protein for cargo transport by the microtubule motor protein kinesin. To investigate the physiological function of JIP3, we examined the effect of Jip3 gene disrupti...

Lysosomes robustly accumulate within axonal swellings at Alzheimer's disease (AD) amyloid plaques. However, the underlying mechanisms and disease relevance of such lysosome accumulations are not well understood. Motivated by these problems, we identified JNK-interacting protein 3 (JIP3) as an important regulator of axonal lysosome transport and maturation. JIP3 knockout mouse neuron primary cul...

The c-Jun NH(2)-terminal kinase (JNK) group of mitogen-activated protein kinases (MAPKs) is activated in response to the treatment of cells with inflammatory cytokines and by exposure to environmental stress. JNK activation is mediated by a protein kinase cascade composed of a MAPK kinase and a MAPK kinase kinase. Here we describe the molecular cloning of a putative molecular scaffold protein, ...

Kinesin motors drive the intracellular transport of multiple cargoes along microtubule tracks; yet, how kinesins discriminate among their many potential cargoes is unknown. We tested whether Kinesin-1 cargoes compete, co-operate or are transported independently of each other. We focused on Kinesin-1 cargoes that bind directly to the kinesin light chain (KLC) subunit, namely the c-Jun NH(2)-term...

Axon branching plays a critical role in establishing the accurate patterning of neuronal circuits in the brain. However, the mechanisms that control axon branching remain poorly understood. Here we report that knockdown of the brain-enriched signaling protein JNK-interacting protein 3 (JIP3) triggers exuberant axon branching and self-contact in primary granule neurons of the rat cerebellar cort...

JNK is a nonreceptor kinase involved in the early events that signal cell migration after injury. However, the linkage to early signals required to initiate the migration response to JNK has not been defined in airway epithelial cells, which exist in an environment subjected to cyclic mechanical strain (MS). The present studies demonstrate that the JNK/stress-activated protein kinase-associated...

Brain-derived neurotrophic factor (BDNF), secreted from target tissues, binds and activates TrkB receptors, located on axonal terminals of the innervating neurons, and thereby initiates retrograde signaling. Long-range anterograde transport of TrkB in axons and dendrites requires kinesin-mediated transport. However, it remains unknown whether anterograde TrkB transport mechanisms are the same i...

Highlighting the importance of proper intracellular organization, many muscle diseases are characterized by mispositioned myonuclei. Proper positioning of myonuclei is dependent upon the microtubule motor proteins, Kinesin-1 and cytoplasmic Dynein, and there are at least two distinct mechanisms by which Kinesin and Dynein move myonuclei. The motors exert forces both directly on the nuclear surf...

In this commentary, Qun Zheng and Michael L. Nonet examine Edwards et al.’s article in which they provide evidence for a domain in invertebrate neurons similar to the vertebrate axonal initial segment that serves to restrict certain organelles from entering the axonal compartment. In their article published in this month’s GENETICS, Edwards et al. (2013) implicate the UNC-16/JIP3/SYD as a criti...