Lysosomal trafficking functions of mucolipin-1 in murine macrophages

Thompson, Eric G.; Schaheen, Lara; Dang, Hope; Fares, Hanna

doi:10.1186/1471-2121-8-54

Cited by 84 publications

(97 citation statements)

References 55 publications

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“…Second, enhanced lysosomal exocytosis was seen in HEK293 cells overexpressing gain-of-function mutant TRPML1 channels ( 66 ). Third, TRPML1 knockdown in a macrophage cell line reduced transport of the major histocompatibility complex II (MHC-II) from lysosomal compartments to the plasma membrane ( 67 ). Fourth, transcription factor EB (TFEB)-induced lysosomal exocytosis (see below) was almost abolished in ML-IV cells ( 27 ).…”

Section: Releasable Lysosome Pool Although Lysosomes Can Undergo Camentioning

confidence: 96%

Lysosomal exocytosis and lipid storage disorders

Samie

2014

Journal of Lipid Research

151

178

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respective smaller building-block molecules: amino acids, monosaccharides, free fatty acids, or nucleotides ( 1-4 ). Hence, since their discovery by Christian De Duve in 1955, lysosomes have been viewed as the cell's degradation center ( 3,5 ). Lysosomes, several hundreds of them in each mammalian cell, are heterogeneous in size (100-1,000 nm) and morphology, and collectively constitute ‫ف‬ 5% of the cell volume ( 6 ). Lysosomes are filled with more than 50 different types of hydrolases: sulphatases, phosphatases, lipases, proteases, carbohydrases, and glycosidases, which effectively catabolize proteins and complex lipids into their building-block molecules ( 1, 4 ). The functions of most lysosomal hydrolytic enzymes require an acidic lumen, which is established and maintained by the vacuolarATPase (V-ATPase)... proton pumps located on the perimeter limited membrane ( 6 ). To protect the perimeter membrane and its resident membrane proteins from degradation, the inner leafl et of the lysosomal membrane is coated with a polysaccharide layer called the glycocalyx ( 7 ).The biomaterials destined for degradation are delivered to lysosomes through endocytic/phagocytic and autophagic pathways ( Fig. 1 ). Endocytosis or phagocytosis of extracellular particles or plasma membrane proteins begins with the invagination of the plasma membrane to form endocytic vesicles, which then undergo a series of maturation processes to fi rst become early endosomes, and then late endosomes [excellently reviewed in ( 5 )] ( Fig. 1 ). In the late endosomes, the destined-to-be-degraded cargo is sorted into the intraluminal vesicles via the endosomal sorting complexes required for transport system ( 5 ). Intraluminal Abstract Lysosomes are acidic compartments in mammalian cells that are primarily responsible for the breakdown of endocytic and autophagic substrates such as membranes, proteins, and lipids into their basic building blocks. Lysosomal storage diseases (LSDs) are a group of metabolic disorders caused by genetic mutations in lysosomal hydrolases required for catabolic degradation, mutations in lysosomal membrane proteins important for catabolite export or membrane traffi cking, or mutations in nonlysosomal proteins indirectly affecting these lysosomal functions. A hallmark feature of LSDs is the primary and secondary excessive accumulation of undigested lipids in the lysosome, which causes lysosomal dysfunction and cell death, and subsequently pathological symptoms in various tissues and organs. There are more than 60 types of LSDs, but an effective therapeutic strategy is still lacking for most of them. Several recent in vitro and in vivo studies suggest that induction of lysosomal exocytosis could effectively reduce the accumulation of the storage materials. Meanwhile, the molecular machinery and regulatory mechanisms for lysosomal exocytosis are beginning to be revealed. In this paper, we fi rst discuss these recent developments with the focus on the functional interactions between lipid storage and lysosomal exocytosis. We th...

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Section: Releasable Lysosome Pool Although Lysosomes Can Undergo Camentioning

confidence: 96%

Lysosomal exocytosis and lipid storage disorders

Samie

2014

Journal of Lipid Research

151

178

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“…All TRPMLs colocalize with lysosome-associated membrane protein (Lamp-1) or Rab7, indicating localization to late endosomes and lysosomes (Karacsonyi et al 2007;Thompson et al 2007;Kim et al 2009b;Martina et al 2009). In addition, TRPML2 is found in recycling endosomes (Karacsonyi et al 2007), whereas TRPML3 also localizes to early endosomes and the plasma membrane (Kim et al 2009b).…”

Section: Trp Channels In Endosomes and Lysosomesmentioning

confidence: 99%

The Role of Transient Receptor Potential Cation Channels in Ca2+ Signaling

Gees

Colsoul²,

Nilius³

2010

Cold Spring Harbor Perspectives in Biology

382

361

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The 28 mammalian members of the super-family of transient receptor potential (TRP) channels are cation channels, mostly permeable to both monovalent and divalent cations, and can be subdivided into six main subfamilies: the TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPP ( polycystin), TRPML (mucolipin), and the TRPA (ankyrin) groups. TRP channels are widely expressed in a large number of different tissues and cell types, and their biological roles appear to be equally diverse. In general, considered as polymodal cell sensors, they play a much more diverse role than anticipated. Functionally, TRP channels, when activated, cause cell depolarization, which may trigger a plethora of voltage-dependent ion channels. Upon stimulation, Ca 2þ permeable TRP channels generate changes in the intracellular Ca 2þ concentration, [Ca 2þ ] i , by Ca 2þ entry via the plasma membrane. However, more and more evidence is arising that TRP channels are also located in intracellular organelles and serve as intracellular Ca 2þ release channels. This review focuses on three major tasks of TRP channels: (1) the function of TRP channels as Ca 2þ entry channels; (2) the electrogenic actions of TRPs; and (3) TRPs as Ca 2þ release channels in intracellular organelles.T ransient receptor potential (TRP) channels constitute a large and functionally versatile family of cation-conducting channel proteins, which have been mainly considered as polymodal unique cell sensors. The first TRP channel gene was discovered in Drosophila melanogaster (Montell and Rubin 1989) in the analysis of a mutant fly whose photoreceptors failed to retain a sustained response to maintained light stimuli. So far, more than 50 TRP channels have been identified with representative members in many species. The evolutionary first TRP channels in protists, chlorophyte algae, choanoflagellates, yeast, and fungi are primary chemo-, thermo-, or mechanosensors (Cai 2008;Wheeler and Brownlee 2008;Chang et al. 2010;Matsuura et al. 2009). Many of these functions are remarkably conserved from protists, worms, and flies to humans (Montell 2005;Pedersen et al. 2005;Nilius et al. 2007;Damann et al. 2008). More than 50 trp genes have been cloned so far that comprise approximately 20% of the known genes encoding ion channels. In mammals, 28 TRP channels were found and classified according to homology into 6 subfamilies: TRPC (canonical), TRPV (vanilloid),

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“…4B,C). Mcoln1 encodes mucolipin 1, which is an endosomal/lysosomal-localized protein required for efficient lysosomal trafficking and lysosomal degradation of endocytosed proteins in RAW264.7 cells (Thompson et al, 2007). We also checked the levels of Fcgamma receptors (FcR) using an antibody that recognizes CD16, CD32 and CD64 (Unkeless, 1979).…”

Section: Journal Of Cell Science 122 (13)mentioning

confidence: 99%

Derlin-dependent accumulation of integral membrane proteins at cell surfaces

Schaheen

Dang

Fares

2009

Journal of Cell Science

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The degradation of misfolded proteins is essential for cellular and organism viability. Quality control mechanisms of protein folding involve multi-component systems, which include chaperones, ubiquitylation enzymes, and ultimately degradation by the proteasome. So far, quality control mechanisms have been described in the cytoplasm, the nucleus and endoplasmic reticulum (ER) (Bader et al., 2007;Goldberg, 2003;Hampton, 2002;Jarosch et al., 2003;Meusser et al., 2005;von Mikecz, 2006).The recognition and degradation of misfolded proteins in the ER is called ER-associated degradation (ERAD) (Hampton, 2002;Jarosch et al., 2003;McCracken and Brodsky, 2003;Meusser et al., 2005;Richly et al., 2005;Sitia and Braakman, 2003). Membrane-spanning and secretory proteins are first transported into the ER in an unfolded state through the Sec61p complex (Matlack et al., 1998). Folding of these nascent polypeptides is assisted by a number of ER-resident chaperones. Translocated proteins also undergo modifications to support folding; these include N-terminal glycosylation and disulphide bond formation (Meusser et al., 2005;Schroder and Kaufman, 2005;Sitia and Braakman, 2003). In the ER, proteins that do not fold properly are retro-translocated to the cytoplasm. During retro-translocation, these misfolded proteins are ubiquitylated by several ER-specific E3 ubiquitin ligase complexes. A cytoplasmic ubiquitin-binding and multi-ubiquitylation enzyme complex further modifies these proteins and finally transports them to the proteasome for degradation.The accumulation of misfolded proteins in the ER activates the unfolded protein response (UPR), which is required for cells to survive conditions of stress. The UPR is mediated by three ER transmembrane proteins, IRE1, PERK and ATF6, which get activated at least in part because of the dissociation of the ER chaperone BiP, to which they are normally bound and also because of their sequestration by misfolded proteins (Bertolotti et al., 2000;Cox et al., 1993;Harding et al., 1999;Haze et al., 1999;Iwawaki et al., 2001;Kimata et al., 2004;Lee et al., 2002;Mori et al., 1993;Okamura et al., 2000). IRE1, PERK and ATF6 function to decrease the load on the ER by reducing translation rate and activating the transcription of chaperones, ERAD proteins and other enzymes. UPR activation also results in increased biosynthesis of some lipids, the elaboration of the ER and increased secretion (Sato et al., 2002;Shaffer et al., 2004;Sriburi et al., 2004). A major downstream regulator of UPR is XBP1/HAC1. Upon activation of IRE1, the XBP1 mRNA is directly spliced by an endonuclease activity in the C-terminus of IRE-1; this splice variant of XBP1 functions as a potent transcriptional activator of several genes (Calfon et al., 2002;Cox and Walter, 1996;Sidrauski and Walter, 1997;Yoshida et al., 2001).Derlin proteins are a conserved family that function in ERAD (Schekman, 2004). They have four transmembrane domains and are conserved in all eukaryotes. There are two members in Saccharomyces cerevisiae, Der1p a...

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Lysosomal trafficking functions of mucolipin-1 in murine macrophages

Cited by 84 publications

References 55 publications

Lysosomal exocytosis and lipid storage disorders

Lysosomal exocytosis and lipid storage disorders

The Role of Transient Receptor Potential Cation Channels in Ca2+ Signaling

Derlin-dependent accumulation of integral membrane proteins at cell surfaces

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