Complex Determinants in Specific Members of the Mannose Receptor Family Govern Collagen Endocytosis

Jürgensen, Henrik J.; Johansson, Karin; Madsen, Daniel H.; Porse, Astrid; Melander, Maria C.; Sørensen, Kristine R.; Nielsen, Christoffer F.; Bugge, Thomas H.; Behrendt, Niels; Engelholm, Lars H.

doi:10.1074/jbc.m113.512780

Cited by 45 publications

(70 citation statements)

References 67 publications

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“…A recent report showed that mouse PLA 2 R did not mediate internalization of rat tail collagen I [16]. In agreement with that report [16], our experiments showed that neither mouse nor human full-length PLA 2 R mediated the internalization of rat tail collagen I ( Fig. 6A and B).…”

Section: Internalization Of Collagen In Hek293 Cells Expressing Pla 2 Rsupporting

confidence: 93%

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C‐type lectin‐like domain and fibronectin‐like type II domain of phospholipase A₂ receptor 1 modulate binding and migratory responses to collagen

Takahashi

Watanabe

et al. 2015

FEBS Letters

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Edited by Beat ImhofKeywords: Phospholipase A 2 receptor 1 Collagen Binding Migration Secretory phospholipase A 2 Fibronectin-like type II domain a b s t r a c t Phospholipase A 2 receptor 1 (PLA 2 R) mediates collagen-dependent migration. The mechanisms by which PLA 2 R interacts with collagen remain unclear. We produced HEK293 cells expressing full-length wild-type PLA 2 R or a truncated PLA 2 R that lacks fibronectin-like type II (FNII) domains or several regions of C-type lectin-like domain (CTLD). We show that the CTLD1-2 as well as the FNII domain of PLA 2 R are responsible for binding to collagen and for collagen-dependent migration. Thus, multiple regions and domains of the extracellular portion of PLA 2 R participate in the responses to collagen. These data suggest a potentially new mechanism for PLA 2 R-mediated biological response beyond that of a receptor for secretory PLA 2 .

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Section: Internalization Of Collagen In Hek293 Cells Expressing Pla 2 Rsupporting

confidence: 93%

“…The mannose receptor, Endo180, and PLA 2 R have collagen binding activity [12][13][14][15][16][17] that is mediated by the FNII domain. FNII domain is the mostly highly conserved sequence in the mannose receptor family [4].…”

Section: Introductionmentioning

confidence: 99%

C‐type lectin‐like domain and fibronectin‐like type II domain of phospholipase A₂ receptor 1 modulate binding and migratory responses to collagen

Takahashi

Watanabe

et al. 2015

FEBS Letters

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“…It has been shown that keratins may undergo a variety of posttranslational modifications, including phosphorylation and glycosylation (35); our results suggest that these modifications may not affect the recognition between keratins and DEC205. Recent evidence shows that the mannose receptor family members might share similar structural features (26)(27)(28)36), but their natural ligands are different. The finding of keratins as the ligands of DEC205 adds more diversity to the receptor-ligand interactions of this family.…”

Section: Discussionmentioning

confidence: 99%

Keratin mediates the recognition of apoptotic and necrotic cells through dendritic cell receptor DEC205/CD205

Cao

Chang

Shi

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Clearance of dead cells is critical for maintaining homeostasis and prevents autoimmunity and inflammation. When cells undergo apoptosis and necrosis, specific markers are exposed and recognized by the receptors on phagocytes. DEC205 (CD205) is an endocytotic receptor on dendritic cells with antigen presentation function and has been widely used in immune therapies for vaccine generation. It has been shown that human DEC205 recognizes apoptotic and necrotic cells in a pH-dependent fashion. However, the natural ligand(s) of DEC205 remains unknown. Here we find that keratins are the cellular ligands of human DEC205. DEC205 binds to keratins specifically at acidic, but not basic, pH through its N-terminal domains. Keratins form intermediate filaments and are important for maintaining the strength of cells and tissues. Our results suggest that keratins also function as cell markers of apoptotic and necrotic cells and mediate a pH-dependent pathway for the immune recognition of dead cells. T he immune system is responsible for removing self-antigens such as dead cells to maintain tissue homeostasis and prevent autoimmunity (1-3). Dead cells are recognized and engulfed by phagocytes through their cell surface receptors (4), leading to either immune activation or tolerance (5-8). A number of receptors have been found to be able to mediate the clearance of dead cells (3); for example, CD14 (9), CD36 (10), integrin (11), PtdSerR (12), CLEC9A (13-15), and TIM receptor family members (16). Among known dead cell markers, phosphatidylserine (PS) is the most common one that can be recognized by several receptors such as CD36, PtdSerR, and TIM receptors, and acts as an "eatme" signal for phagocytes mediating dead cell clearance (4). Other than PS, several cellular proteins have also been found to be able to perform the similar function. For example, actin filaments can be recognized by CLEC9A as a damaged cell marker (13, 15). The recognition of different dead cell markers by phagocytes provides an efficient way to remove cell debris completely.Keratins are important cytoskeletal components and form intermediate filaments in cytoplasm. There are 54 known members in the keratin family that are divided into two types based on their isoelectric points and sequences (17). Keratin monomers can assemble into bundles first and then form fibrous filaments ∼10 nm in diameter, which act as a scaffold and provide mechanical support for maintaining the strength and toughness of cells and tissues (18,19). Recently, evidence has accumulated showing that keratins play physiological roles in addition to their structural functions, for example, in cell growth, proliferation, mobility, apoptosis, and tumorigenesis (18,20,21). DEC205 (CD205 or Ly75, molecular mass of 205 kDa) is an endocytotic receptor highly expressed on dendritic cells and thymic epithelial cells (8,22) and capable of inducing either tolerance or immunity in the absence or presence of inflammatory stimuli (23). DEC205 belongs to the mannose receptor family (24), which includes...

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“…Characteristically this family of proteins includes an N-terminal, cysteine-rich/ricin B like domain, a fibronectin type II domain, and a series of 8-10 C-type lectin-like domains. This mesenchymal cell surface receptor has an important function in collagen internalization [38][39][40]. In addition, uPARAP/Endo180 was shown to aid in the initial adhesion of fibroblasts to collagen and to accelerate the migration of these cells on a fibrillar collagen matrix [38,39,41,42].…”

Section: Uparap/endo180mentioning

confidence: 99%

Collagen Type I as a Ligand for Receptor-Mediated Signaling

et al. 2017

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Collagens form the fibrous component of the extracellular matrix in all multi-cellular animals. Collagen type I is the most abundant collagen present in skin, tendons, vasculature, as well as the organic portion of the calcified tissue of bone and teeth. This review focuses on numerous receptors for which collagen acts as a ligand, including integrins, discoidin domain receptors DDR1 and 2, OSCAR, GPVI, G6b-B, and LAIR-1 of the leukocyte receptor complex (LRC) and mannose family receptor uPARAP/Endo180. We explore the process of collagen production and self-assembly, as well as its degradation by collagenases and gelatinases in order to predict potential temporal and spatial sites of action of different collagen receptors. While the interactions of the mature collagen matrix with integrins and DDR are well-appreciated, potential signals from immature matrix as well as collagen degradation products are possible but not yet described. The role of multiple collagen receptors in physiological processes and their contribution to pathophysiology of diseases affecting collagen homeostasis require further studies.

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Complex Determinants in Specific Members of the Mannose Receptor Family Govern Collagen Endocytosis

Cited by 45 publications

References 67 publications

C‐type lectin‐like domain and fibronectin‐like type II domain of phospholipase A₂ receptor 1 modulate binding and migratory responses to collagen

C‐type lectin‐like domain and fibronectin‐like type II domain of phospholipase A₂ receptor 1 modulate binding and migratory responses to collagen

Keratin mediates the recognition of apoptotic and necrotic cells through dendritic cell receptor DEC205/CD205

Collagen Type I as a Ligand for Receptor-Mediated Signaling

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Complex Determinants in Specific Members of the Mannose Receptor Family Govern Collagen Endocytosis

Cited by 45 publications

References 67 publications

C‐type lectin‐like domain and fibronectin‐like type II domain of phospholipase A2 receptor 1 modulate binding and migratory responses to collagen

C‐type lectin‐like domain and fibronectin‐like type II domain of phospholipase A2 receptor 1 modulate binding and migratory responses to collagen

Keratin mediates the recognition of apoptotic and necrotic cells through dendritic cell receptor DEC205/CD205

Collagen Type I as a Ligand for Receptor-Mediated Signaling

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C‐type lectin‐like domain and fibronectin‐like type II domain of phospholipase A₂ receptor 1 modulate binding and migratory responses to collagen

C‐type lectin‐like domain and fibronectin‐like type II domain of phospholipase A₂ receptor 1 modulate binding and migratory responses to collagen