Novel pathways, membrane coats and PI kinase regulation in yeast lysosomal trafficking

1998 ◽  
Vol 9 (5) ◽  
pp. 527-533 ◽  
Author(s):  
Christopher G. Burd ◽  
Markus Babst ◽  
Scott D. Emr
Keyword(s):  
Lysosomal Trafficking ◽  
Kinase Regulation ◽  
Pi Kinase

scholarly journals Making connections: control of PI kinase signaling at ER‐PM junctions (351.3)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Andrew Manford ◽  
Scott Emr ◽  
Christopher Stefan
Keyword(s):  
Kinase Signaling ◽  
Pi Kinase

scholarly journals Molecular Dissection of Receptor Tyrosine Kinase Regulation by Cbl Proteins

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Gulzar Ahmad ◽  
Alagarsamy L Reddi ◽  
Mayumi Naramura ◽  
Hamid Band
Keyword(s):  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Molecular Dissection ◽  
Kinase Regulation ◽  
Cbl Proteins

scholarly journals Lysosomal trafficking regulator Lyst links membrane trafficking to toll-like receptor–mediated inflammatory responses

2016 ◽  
Vol 214 (1) ◽  
pp. 227-244 ◽  
Author(s):  
Andreas Westphal ◽  
Weijia Cheng ◽  
Jinbo Yu ◽  
Guntram Grassl ◽  
Martina Krautkrämer ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Membrane Trafficking ◽  
Inflammatory Responses ◽  
Functional Integration ◽  
Receptor Signaling ◽  
Toll Like Receptor ◽  
Tlr Signaling ◽  
Lysosomal Trafficking ◽  
Phagosomal Maturation ◽  
Chediak Higashi Syndrome

Subcellular compartmentalization of receptor signaling is an emerging principle in innate immunity. However, the functional integration of receptor signaling pathways into membrane trafficking routes and its physiological relevance for immune responses is still largely unclear. In this study, using Lyst-mutant beige mice, we show that lysosomal trafficking regulator Lyst links endolysosomal organization to the selective control of toll-like receptor 3 (TLR3)– and TLR4-mediated proinflammatory responses. Consequently, Lyst-mutant mice showed increased susceptibility to bacterial infection and were largely resistant to endotoxin-induced septic shock. Mechanistic analysis revealed that Lyst specifically controls TLR3- and TLR4-induced endosomal TRIF (TIR domain–containing adapter-inducing interferon β) signaling pathways. Loss of functional Lyst leads to dysregulated phagosomal maturation, resulting in a failure to form an activation-induced Rab7+ endosomal/phagosomal compartment. This specific Rab7+ compartment was further demonstrated to serve as a major site for active TRIF signaling events, thus linking phagosomal maturation to specific TLR signaling pathways. The immunoregulatory role of Lyst on TLR signaling pathways was confirmed in human cells by CRISPR/Cas9-mediated gene inactivation. As mutations in LYST cause human Chédiak-Higashi syndrome, a severe immunodeficiency, our findings also contribute to a better understanding of human disease mechanisms.

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