Isolation and analysis of the human 46‐kDa mannose 6‐phosphate receptor gene

Klier, Hans‐Jürgen; Figura, Kurt Von; Pohlmann, R

doi:10.1111/j.1432-1033.1991.tb15877.x

Cited by 21 publications

(6 citation statements)

References 21 publications

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“…The Golgi lumens were swollen in HeLa cells and less pronouncedly in U2OS cells compared to those in the control cells, something also observed to a lesser extent in CQ-treated cells. Therefore, we also examined the distribution of M6PR (mannose-6-phosphate receptor, cation dependent), a protein cycling between the TGN and endosomes [39,40]. In agreement with the other observations, M6PR changed distribution in the presence of CQ, becoming more dispersed in punctate structures, whereas BafA 1 had no effect on the subcellular localization of this protein (Figure 3(D)).…”

Section: Cq Affects the Morphology Of Degradative Compartments Differsupporting

confidence: 86%

Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion

et al. 2018

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Macroautophagy/autophagy is a conserved transport pathway where targeted structures are sequestered by phagophores, which mature into autophagosomes, and then delivered into lysosomes for degradation. Autophagy is involved in the pathophysiology of numerous diseases and its modulation is beneficial for the outcome of numerous specific diseases. Several lysosomal inhibitors such as bafilomycin A (BafA), protease inhibitors and chloroquine (CQ), have been used interchangeably to block autophagy in in vitro experiments assuming that they all primarily block lysosomal degradation. Among them, only CQ and its derivate hydroxychloroquine (HCQ) are FDA-approved drugs and are thus currently the principal compounds used in clinical trials aimed to treat tumors through autophagy inhibition. However, the precise mechanism of how CQ blocks autophagy remains to be firmly demonstrated. In this study, we focus on how CQ inhibits autophagy and directly compare its effects to those of BafA. We show that CQ mainly inhibits autophagy by impairing autophagosome fusion with lysosomes rather than by affecting the acidity and/or degradative activity of this organelle. Furthermore, CQ induces an autophagy-independent severe disorganization of the Golgi and endo-lysosomal systems, which might contribute to the fusion impairment. Strikingly, HCQ-treated mice also show a Golgi disorganization in kidney and intestinal tissues. Altogether, our data reveal that CQ and HCQ are not bona fide surrogates for other types of late stage lysosomal inhibitors for in vivo experiments. Moreover, the multiple cellular alterations caused by CQ and HCQ call for caution when interpreting results obtained by blocking autophagy with this drug.

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Section: Cq Affects the Morphology Of Degradative Compartments Differsupporting

confidence: 86%

Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion

et al. 2018

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“…This contrast suggests that CDMPR plays important roles in lysosomal enzyme trafficking in non-hepatocyte cells of the liver. Promoter analyses of human and mouse CDMPR genes have shown that they contain CpG islands and lack a TATA box, suggesting that CDMPR is expressed constitutively as a housekeeping gene (Klier et al 1991;Ludwig et al 1992), whereas the expression of CIMPR is regulated by several transcription factors (Liu et al 1995). Such gene characteristics of CDMPR may correspond with its rather broad expression in rat liver tissue.…”

Section: Discussionmentioning

confidence: 99%

Different Distribution Patterns of the Two Mannose 6-phosphate Receptors in Rat Liver

Waguri

Kohmura

Kanamori

et al. 2001

J Histochem Cytochem.

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Two mannose 6-phosphate receptors, cation-dependent and -independent receptors (CDMPR and CIMPR), play an important role in the intracellular transport of lysosomal enzymes. To investigate functional differences between the two in vivo, their distribution was examined in the rat liver using immunohistochemical techniques. Positive signals corresponding to CIMPR were detected intensely in hepatocytes and weakly in sinusoidal Kupffer cells and interstitial cells in Glisson's capsule. In the liver acinus, hepatocytes in the perivenous region showed a more intense immunoreactivity than those in the periportal region. On the other hand, positive staining of CDMPR was detected at a high level in Kupffer cells, epithelial cells of interlobular bile ducts, and fibroblast-like cells, but the corresponding signal was rather weak in hepatocytes. In situ hybridization analysis also revealed a high level of expression of CIMPR mRNAs in hepatocytes and of CDMPR mRNA in Kupffer cells. By double immunostaining, OX6-positive antigen-presenting cells in Glisson's capsule were co-labeled with the CDMPR signal but were only faintly stained with anti-CIMPR. These different distribution patterns of the two MPRs suggest distinct functional properties of each receptor in liver tissue.

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“…In fact, the extracytoplasmic domain of CD-M6PR is homologous to the approximately 145 amino acid long repeating domains present in the CI-M6PR with sequence identity *Address correspondence to this author at the Inserm unité 826, Bâtiment recherche, CRLC Val d'Aurelle, 34298 Montpellier, France; E-mail: m.garcia@valdorel.fnclcc.fr ranging from 14 to 28%. These studies allowed to conclude that these two receptors located on different chromosomes (12p13 and 6q26, respectively) have diverged from a common ancestral gene [13,14].…”

Section: Structure Of Mannose 6-phosphate Receptors and Ligand Multipmentioning

confidence: 97%

Mannose 6-Phosphate Receptor Targeting and its Applications in Human Diseases

Gary‐Bobo

Nirdé²,

Jeanjean³

et al. 2007

CMC

159

112

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The cation-independent mannose 6-phosphate receptor is a multifunctional protein which binds at the cell surface to two distinct classes of ligands, the mannose 6-phosphate (M6P) bearing proteins and IGF-II. Its major function is to bind and transport M6P-enzymes to lysosomes, but it can also modulate the activity of a variety of extracellular M6P-glycoproteins (i.e., latent TGFbeta precursor, urokinase-type plasminogen activator receptor, Granzyme B, growth factors, Herpes virus). The purpose of this review is to highlight the synthesis and potential use of high affinity M6P analogues able to target this receptor. Several M6P analogues with phosphonate, carboxylate or malonate groups display a higher affinity and a stronger stability in human serum than M6P itself. These derivatives could be used to favour the delivery of specific therapeutic compounds to lysosomes, notably in enzyme replacement therapies of lysosomal diseases or in neoplastic drug targeting. In addition, their potential applications in preventing clinical disorders, which are associated with the activities of other M6P-proteins involved in wound healing, cell growth or viral infection, will be discussed.

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Isolation and analysis of the human 46‐kDa mannose 6‐phosphate receptor gene

Cited by 21 publications

References 21 publications

Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion

Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion

Different Distribution Patterns of the Two Mannose 6-phosphate Receptors in Rat Liver

Mannose 6-Phosphate Receptor Targeting and its Applications in Human Diseases

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