Kinesin-Dependent Axonal Transport Is Mediated by the Sunday Driver (SYD) Protein

Bowman, Aaron B.; Kamal, Adeela; Ritchings, Bruce W.; Philp, Alastair Valentine; McGrail, Maura; Gindhart, Joseph G.; Goldstein, Lawrence S.B.

doi:10.1016/s0092-8674(00)00162-8

Cited by 305 publications

(369 citation statements)

References 36 publications

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“…One is a homologue of JNK3 (MAPK10 isoform-3). We focused on the possibility that JNK3 may be a MyD88-5 binding partner because of the reported association of JNKs with mitochondria ( 37 ) and microtubules ( 38,39 ). Interest in the candidacy of JNK3 was heightened further by its important role in regulating neuronal death during stress ( 40 -46 ).…”

Section: Myd88-5 Is Associated With Mitochondriamentioning

confidence: 99%

MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival

Kim¹,

Zhou²,

Qian³

et al. 2007

J Cell Biol

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Section: Myd88-5 Is Associated With Mitochondriamentioning

confidence: 99%

MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival

Kim¹,

Zhou²,

Qian³

et al. 2007

J Cell Biol

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“…Motor protein binding and transport of cargoes intracellularly sometimes utilizes a set of proteins involved in cell signaling (Bowman et al, 2000;Goldstein, 2001). For example, the Jun N-terminal kinase (JNK)-interacting proteins (JIPs) are thought to serve as scaffolding proteins for the JNK signaling pathway (Davis, 2000).…”

Section: Introductionmentioning

confidence: 99%

“…Four light intermediate chains (LICs) and several dynein light chains (DLCs) also seem to be involved in imparting proper cargo selection. Finally, a variety of receptor systems and transporters have been shown to bind to molecular motors, either directly through the light chains (LCs), or through motor receptors or adaptor proteins (Klopfenstein et al, 2000;Kamal and Goldstein, 2002;Karcher et al, 2002).Motor protein binding and transport of cargoes intracellularly sometimes utilizes a set of proteins involved in cell signaling (Bowman et al, 2000;Goldstein, 2001). For example, the Jun N-terminal kinase (JNK)-interacting proteins (JIPs) are thought to serve as scaffolding proteins for the JNK signaling pathway (Davis, 2000).…”

mentioning

confidence: 99%

A Novel Transforming Growth Factor-β Receptor-interacting Protein That Is Also a Light Chain of the Motor Protein Dynein

Tang¹,

Staub²,

Gao

et al. 2002

MBoC

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The phosphorylated, activated cytoplasmic domains of the transforming growth factor-␤ (TGF␤) receptors were used as probes to screen an expression library that was prepared from a highly TGF␤-responsive intestinal epithelial cell line. One of the TGF␤ receptor-interacting proteins isolated was identified to be the mammalian homologue of the LC7 family (mLC7) of dynein light chains (DLCs). This 11-kDa cytoplasmic protein interacts with the TGF␤ receptor complex intracellularly and is phosphorylated on serine residues after ligand-receptor engagement. Forced expression of mLC7-1 induces specific TGF␤ responses, including an activation of Jun N-terminal kinase (JNK), a phosphorylation of c-Jun, and an inhibition of cell growth. Furthermore, TGF␤ induces the recruitment of mLC7-1 to the intermediate chain of dynein. A kinase-deficient form of TGF␤ RII prevents both mLC7-1 phosphorylation and interaction with the dynein intermediate chain (DIC). This is the first demonstration of a link between cytoplasmic dynein and a natural growth inhibitory cytokine. Furthermore, our results suggest that TGF␤ pathway components may use a motor protein light chain as a receptor for the recruitment and transport of specific cargo along microtublules. INTRODUCTIONTransforming growth factor-␤ (TGF␤) is the prototype for the TGF␤ superfamily of highly conserved growth regulatory polypeptides that also includes the activins, inhibins, bone morphogenetic proteins, decapentaplegic (Dpp), nodal, Lefty, and others (Roberts, 1998;Sporn and Vilcek, 2000;Yue and Mulder, 2001). Alterations in the TGF␤ signaling components and pathways have been implicated in a vast array of human pathologies, including cancer (Massague et al., 2000;Sporn and Vilcek, 2000;Derynck et al., 2001).TGF␤ binds to two types of transmembrane serine/threonine kinase receptors (RI and RII) in a heterotetrameric complex, to activate downstream components (Roberts, 1998; Massague et al., 2000;Sporn and Vilcek, 2000;Yue and Mulder, 2001). The Smad family of signaling intermediates plays an important role in mediating TGF␤ responses (Attisano and Wrana, 2000;ten Dijke et al., 2000;Yue and Mulder, 2001). Moreover, TGF␤ has been shown to regulate Ras (Mulder and Morris, 1992;Hartsough et al., 1996;Yue et al., 1998) and several components of the mitogen-activated protein kinase (Mapk) pathways (Hartsough and Mulder, 1995;Frey and Mulder, 1997;Mulder, 2000;Sporn and Vilcek, 2000;Yue and Mulder, 2001). In addition to the Ras/Mapk and Smad pathways, several proteins have been identified based upon their interaction with the TGF␤ receptors (Yue and Mulder, 2001). Furthermore, various Smad-interacting proteins have also been identified, including SARA and Dab2, which interact with both Smads and the TGF␤ receptors (Tsukazaki et al., 1998;Hocevar et al., 2001;Yue and Mulder, 2001).Despite advances in our understanding of the mechanisms by which the Smad and Ras/Mapk cascades mediate some TGF␤ effects, these pathways seem to regulate primarily transcriptional events (Hocevar et al., 1...

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“…14 Moreover, loss-offunction mutations of the genes encoding Drosophila Sunday Driver (JSAP1/JIP3) or Caenorhabditis elegans UNC-16 (JSAP1/JIP3) result in mislocalized axonal cargoes, a phenotype similar to that of kinesin-1 mutants in these organisms. 15,16 Although mammalian JIPs also seem to be involved in the cargo transport in axons, their roles in this transport remain fragmentary, with several studies reporting inconsistent results. No mislocalization of axonal cargoes, including mitochondria and the synaptic-vesicle marker synapsin, was detected in Jip1 and Jip2 double-knockout (dKO) neurons.…”

mentioning

confidence: 99%

JSAP1/JIP3 and JLP regulate kinesin-1-dependent axonal transport to prevent neuronal degeneration

et al. 2015

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Axonal transport is critical for neuronal development and function, and defective axonal transport has been implicated in neurodegenerative diseases. However, how axonal transport is regulated, or how defective transport leads to neuronal degeneration, remains unclear. Here, we report that c-Jun NH 2 -terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1, also known as JNK-interacting protein 3 (JIP3)) and JNK-associated leucine zipper protein (JLP) are essential for postnatal brain development. Mice with a double-knockout (dKO) in Jsap1 and Jlp in the dorsal telencephalon developed progressive neuron loss. Using a primary neuron culture system with induced disruption of targeted genes, combined with gene rescue experiments, we show that JSAP1 and JLP regulate kinesin-1-dependent axonal transport with functional redundancy. We also show that the binding of JSAP1 and JLP to kinesin-1 heavy chain is crucial for interactions between kinesin-1 and microtubules. Furthermore, we describe a molecular mechanism by which defective kinesin-1-dependent axonal transport in Jsap1:Jlp dKO neurons causes axonal degeneration and subsequent neuronal death. JNK hyperactivation because of increased intra-axonal Ca 2+ in the Jsap1:Jlp dKO neurons was found to mediate both the axonal degeneration and neuronal death, in cooperation with the Ca 2+ -dependent protease calpain. Our results indicate that axonal JNK may relocate to the nucleus in a dynein-dependent manner, where it activates the transcription factor c-Jun, resulting in neuronal death. Taken together, our data establish JSAP1 and JLP as positive regulators of kinesin-1-dependent axonal transport, which prevents neuronal degeneration.

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Kinesin-Dependent Axonal Transport Is Mediated by the Sunday Driver (SYD) Protein

Cited by 305 publications

References 36 publications

MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival

MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival

A Novel Transforming Growth Factor-β Receptor-interacting Protein That Is Also a Light Chain of the Motor Protein Dynein

JSAP1/JIP3 and JLP regulate kinesin-1-dependent axonal transport to prevent neuronal degeneration

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