Interaction of the Unc-51-like kinase and microtubule-associated protein light chain 3 related proteins in the brain: possible role of vesicular transport in axonal elongation

Okazaki, Naoaki; Yan, Jin; Yuasa, Shigeki; Ueno, Takashi; Kominami, Eiki; Masuho, Yasuhiko; Koga, Hisashi; Muramatsu, Masaaki

doi:10.1016/s0169-328x(00)00218-7

Cited by 128 publications

(116 citation statements)

References 46 publications

Supporting

Mentioning

112

Contrasting

Unclassified

Order By: Relevance

“…Given that ULK1 interacts with multiple proteins (Okazaki et al, 2000;Tomoda et al, 2004), the starvation-induced phosphorylations might alter a protein-protein interaction mediated by ULK. Alternatively, the phosphorylations might have effects on the catalytic activity or localization to autophagosomes of ULK.…”

Section: Discussionmentioning

confidence: 99%

“…The ULK1 C-terminus is also involved in binding SynGAP and syntenin the proteins regulating the neuronal axon outgrowth, and is important for the autophagosomal localization of ULK1 (Tomoda et al, 2004;Chan et al, 2007). ULK1 also interacts with GATE-16 and GABARAP, the mammalian homologues of Atg8 that localize to autophagosome (Okazaki et al, 2000;Kabeya et al, 2004). Given that ULK1 binds multiple proteins that localize to autophagosomes, it may be possible that ULK1 regulates the autophagosomal localization of the binding proteins.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

ULK-Atg13-FIP200 Complexes Mediate mTOR Signaling to the Autophagy Machinery

Jung

Jun

et al. 2009

MBoC

1,725

1,600

View full text Add to dashboard Cite

Autophagy, the starvation-induced degradation of bulky cytosolic components, is up-regulated in mammalian cells when nutrient supplies are limited. Although mammalian target of rapamycin (mTOR) is known as the key regulator of autophagy induction, the mechanism by which mTOR regulates autophagy has remained elusive. Here, we identify that mTOR phosphorylates a mammalian homologue of Atg13 and the mammalian Atg1 homologues ULK1 and ULK2. The mammalian Atg13 binds both ULK1 and ULK2 and mediates the interaction of the ULK proteins with FIP200. The binding of Atg13 stabilizes and activates ULK and facilitates the phosphorylation of FIP200 by ULK, whereas knockdown of Atg13 inhibits autophagosome formation. Inhibition of mTOR by rapamycin or leucine deprivation, the conditions that induce autophagy, leads to dephosphorylation of ULK1, ULK2, and Atg13 and activates ULK to phosphorylate FIP200. These findings demonstrate that the ULK-Atg13-FIP200 complexes are direct targets of mTOR and important regulators of autophagy in response to mTOR signaling.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

ULK-Atg13-FIP200 Complexes Mediate mTOR Signaling to the Autophagy Machinery

Jung

Jun

et al. 2009

MBoC

1,725

1,600

View full text Add to dashboard Cite

show abstract

“…Interestingly, the mammalian Atg8 orthologs, GATE-16, GABARAP, and to a lesser degree LC3, have also been shown to interact with ULK1 in a similar region of the PS domain, between amino acids 287 and 416. 22 A second quality shared by yeast and human Atg13 is that human Atg13 is a phosphoprotein, as manifested by 32 PO 4 incorporation and a reduced mobility during SDS-PAGE (Fig. 5).…”

Section: Discussionmentioning

confidence: 99%

“…Known ULK1-interacting proteins include GATE-16, GABARAP, SynGAP, Syntenin, p62/SQSTM1 and FIP200. [22][23][24][25] FIP200, which binds multiple proteins and regulates various cellular functions, 26 is particularly interesting in that it is essential for autophagy, modulates ULK1 activity, and has coiled-coil domains, making FIP200 a potential Atg17 ortholog. 24 Regarding Atg13, a gapped-blast search of fungal, plant and human databases identified the uncharacterized protein FLJ20698 as a potential human ortholog of Atg13.…”

Section: Introductionmentioning

confidence: 99%

A novel, human Atg13 binding protein, Atg101, interacts with ULK1 and is essential for macroautophagy

Mercer

Kaliappan²,

Dennis³

2009

Autophagy

371

321

View full text Add to dashboard Cite

Macroautophagy is an intracellular, vesicle-mediated mechanism for the sequestration and ultimate lysosomal degradation of cytoplasmic proteins, organelles and macromolecules. The macroautophagy process and many of the autophagy-specific (Atg) proteins are remarkably well conserved in higher eukaryotes. In yeast, the Atg1 kinase complex includes Atg1, Atg13, Atg17, and at least four other interacting proteins, some of which are phosphorylated in a TOR-dependent manner, placing the Atg1 signaling complex downstream of a major nutrient-sensing pathway. Atg1 orthologs, including mammalian unc-51-like kinase 1 (ULK1), have been identified in higher eukaryotes and have been functionally linked to autophagy. This suggests that other components of the Atg1 complex exist in higher eukaryotes. Recently, a putative human Atg13 ortholog, FLJ20698, was identified by gapped-BLAST analysis. We show here that FLJ20698 (Atg13) is a ULK1-interacting phosphoprotein that is essential for macroautophagy. Furthermore, we identify a novel, human Atg13-interacting protein, FLJ11773, which we have termed Atg101. Atg101 is essential for autophagy and interacts with ULK1 in an Atg13-dependent manner. Additionally, we present evidence that intracellular localization of the ULK1 complex is regulated by nutrient conditions. Finally, we demonstrate that Atg101 stabilizes the expression of Atg13 in the cell, suggesting that Atg101 contributes to Atg13 function by protecting Atg13 from proteasomal degradation. Therefore, the identification of the novel protein, Atg101, and the validation of Atg13 and Atg101 as ULK1-interacting proteins, suggests an Atg1 complex is involved in the induction of macroautophagy in mammalian cells.

show abstract

“…Mutations that impair growth cone functions, such as unc-51 (Ogura et al, 1994;Okazaki et al, 2000) and unc-73 (Steven et al, 1998(Steven et al, , 2005, usually caused the highest incidence of defects and truncations in the distal end of the M2 neurons (within the metacorpus), as well as defects in the lengths of the two major processes of the NSM neurons. The unc-6/netrin pathway is important for circumferential and anteroposterior guidance decisions in C. elegans (Hedgecock et al, Outline of the pharynx in which the trajectories of the M2L and NSML neurons are drawn, together with M3R of which only the cell body is shown for clarity.…”

Section: Growth Cones Guidance Pathways and Robustnessmentioning

confidence: 99%

Fishing lines, time‐delayed guideposts, and other tricks used by developing pharyngeal neurons in Caenorhabditis elegans

Pilon

2008

Developmental Dynamics

View full text Add to dashboard Cite

The 20 neurons that innervate the Caenorhabditis elegans pharynx form a simple nervous system that develops and operates in near complete isolation from the rest of the worm body and, therefore, offers a manageable degree of complexity for developmental genetics studies. This review discusses the progress that has been made in determining the mechanisms by which 4 of the 20 pharyngeal neurons develop, and emphasizes surprising processes that add to the classic growth cone guidance model which is usually thought to explain how most axons establish their trajectories.

show abstract

Interaction of the Unc-51-like kinase and microtubule-associated protein light chain 3 related proteins in the brain: possible role of vesicular transport in axonal elongation

Cited by 128 publications

References 46 publications

ULK-Atg13-FIP200 Complexes Mediate mTOR Signaling to the Autophagy Machinery

ULK-Atg13-FIP200 Complexes Mediate mTOR Signaling to the Autophagy Machinery

A novel, human Atg13 binding protein, Atg101, interacts with ULK1 and is essential for macroautophagy

Fishing lines, time‐delayed guideposts, and other tricks used by developing pharyngeal neurons in Caenorhabditis elegans

Contact Info

Product

Resources

About