Sunday Driver Interacts with Two Distinct Classes of Axonal Organelles

Abstract

The extreme polarized morphology of neurons poses a challenging problem for intracellular trafficking pathways. The distant synaptic terminals must communicate via axonal transport with the cell soma for neuronal survival, function, and repair. Multiple classes of organelles transported along axons may establish and maintain the polarized morphology of neurons, as well as control signaling and neuronal responses to extracellular cues such as neurotrophic or stress factors. We reported previously that the motorbinding protein Sunday Driver (syd), also known as JIP3 or JSAP1, links vesicular axonal transport to injury signaling. To better understand syd function in axonal transport and in the response of neurons to injury, we developed a purification strategy based on anti-syd antibodies conjugated to magnetic beads to identify sydassociated axonal vesicles. Electron microscopy analyses revealed two classes of syd-associated vesicles of distinct morphology. To identify the molecular anatomy of syd vesicles, we determined their protein composition by mass spectrometry. Gene Ontology analyses of each vesicle protein content revealed their unique identity and indicated that one class of syd vesicles belongs to the endocytic pathway, whereas another may belong to an anterogradely transported vesicle pool. To validate these findings, we examined the transport and localization of components of syd vesicles within axons of mouse sciatic nerve. Together, our results lead us to propose that endocytic syd vesicles function in part to carry injury signals back to the cell body, whereas anterograde syd vesicles may play a role in axonal outgrowth and guidance.

Fast axonal transport of the proteasome complex depends on membrane interaction and molecular motor function

“…5C,D). As expected, we also observed enrichment in this fraction of synaptic transmembrane proteins -synaptotagmin and synaptophysin (SPH, also known as SYP) -as well as kinesin and dynein motors (Abe et al, 2009) (Fig. 5C,D).…”

“…Purification of synaptosomes has been described previously (Abe et al, 2009). Briefly, homogenized mouse brain cortices treated at 4˚C (0.3 M sucrose, 4 mM HEPES pH 7.5 and protease inhibitors) were centrifuged for 10 minutes, 800 g, to obtain a P1 pellet and S1 supernatant.…”

Syntaxin13 Expression Is Regulated by Mammalian Target of Rapamycin (mTOR) in Injured Neurons to Promote Axon Regeneration

“…Syntaxin13 localizes to bi-directional endosomes carrying the scaffolding protein JIP3 on their surface (57), and JIP3 retrograde transport has been implicated in the regenerative response (58,59).…”

JNK/stress-activated protein kinase associated protein 1 is required for early development of telencephalic commissures in embryonic brains

“…JSAP1 also interact with focal adhesion kinase (FAK), which is activated during cell adhesive interactions with the extracellular matrix (Takino et al, 2002(Takino et al, , 2005. Moreover, JSAP1 is distributed in growth cones and plasma membrane as well as in the soma of neurons during development (Kelkar et al, 2000;Sato et al, 2004Sato et al, , 2008Sato et al, , 2011Abe et al, 2009). Thus, these findings indicate that JSAP1 has a function to regulate axonal development.…”