PMID- 32424040
OWN - NLM
STAT- MEDLINE
DCOM- 20210111
LR  - 20240329
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 295
IP  - 27
DP  - 2020 Jul 3
TI  - The collagen receptor uPARAP/Endo180 regulates collectins through unique 
      structural elements in its FNII domain.
PG  - 9157-9170
LID - S0021-9258(17)50336-1 [pii]
LID - 10.1074/jbc.RA120.013710 [doi]
AB  - C-type lectins that contain collagen-like domains are known as collectins. These 
      proteins are present both in the circulation and in extravascular compartments 
      and are central players of the innate immune system, contributing to first-line 
      defenses against viral, bacterial, and fungal pathogens. The collectins 
      mannose-binding lectin (MBL) and surfactant protein D (SP-D) are regulated by 
      tissue fibroblasts at extravascular sites via an endocytic mechanism governed by 
      urokinase plasminogen activator receptor-associated protein (uPARAP or Endo180), 
      which is also a collagen receptor. Here, we investigated the molecular mechanisms 
      that drive the uPARAP-mediated cellular uptake of MBL and SP-D. We found that the 
      uptake depends on residues within a protruding loop in the fibronectin type-II 
      (FNII) domain of uPARAP that are also critical for collagen uptake. Importantly, 
      however, we also identified FNII domain residues having an exclusive role in 
      collectin uptake. We noted that these residues are absent in the related collagen 
      receptor, the mannose receptor (MR or CD206), which consistently does not 
      interact with collectins. We also show that the second C-type lectin-like domain 
      (CTLD2) is critical for the uptake of SP-D, but not MBL, indicating an additional 
      level of complexity in the interactions between collectins and uPARAP. Finally, 
      we demonstrate that the same molecular mechanisms enable uPARAP to engage MBL 
      immobilized on the surface of pathogens, thereby expanding the potential 
      biological implications of this interaction. Our study reveals molecular details 
      of the receptor-mediated cellular regulation of collectins and offers critical 
      clues for future investigations into collectin biology and pathology.
CI  - (c) 2020 Norregaard et al.
FAU - Norregaard, Kirstine Sandal
AU  - Norregaard KS
AD  - Finsen Laboratory, Rigshospitalet/Biotech Research and Innovation Center, 
      University of Copenhagen, Copenhagen N, Denmark.
FAU - Krigslund, Oliver
AU  - Krigslund O
AD  - Finsen Laboratory, Rigshospitalet/Biotech Research and Innovation Center, 
      University of Copenhagen, Copenhagen N, Denmark.
FAU - Behrendt, Niels
AU  - Behrendt N
AD  - Finsen Laboratory, Rigshospitalet/Biotech Research and Innovation Center, 
      University of Copenhagen, Copenhagen N, Denmark.
FAU - Engelholm, Lars H
AU  - Engelholm LH
AD  - Finsen Laboratory, Rigshospitalet/Biotech Research and Innovation Center, 
      University of Copenhagen, Copenhagen N, Denmark.
FAU - Jurgensen, Henrik Jessen
AU  - Jurgensen HJ
AD  - Finsen Laboratory, Rigshospitalet/Biotech Research and Innovation Center, 
      University of Copenhagen, Copenhagen N, Denmark. Electronic address: 
      hjj@finsenlab.dk.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200518
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Carrier Proteins)
RN  - 0 (Collectins)
RN  - 0 (Endo180)
RN  - 0 (Lectins, C-Type)
RN  - 0 (MBL2 protein, human)
RN  - 0 (Mannose Receptor)
RN  - 0 (Mannose-Binding Lectin)
RN  - 0 (Mannose-Binding Lectins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Pulmonary Surfactant-Associated Protein D)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Collagen)
RN  - 0 (Receptors, Mitogen)
RN  - 0 (Receptors, Urokinase Plasminogen Activator)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Animals
MH  - CHO Cells
MH  - Carrier Proteins/metabolism
MH  - Collagen/metabolism
MH  - Collectins/*metabolism
MH  - Cricetulus
MH  - Endocytosis/*physiology
MH  - Fibroblasts/metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Lectins, C-Type
MH  - Mannose Receptor
MH  - Mannose-Binding Lectin/metabolism
MH  - Mannose-Binding Lectins
MH  - Membrane Glycoproteins/metabolism
MH  - Pulmonary Surfactant-Associated Protein D/metabolism
MH  - Receptors, Cell Surface
MH  - Receptors, Collagen/metabolism
MH  - Receptors, Mitogen/*genetics/metabolism
MH  - Receptors, Urokinase Plasminogen Activator/genetics/metabolism
PMC - PMC7335807
OTO - NOTNLM
OT  - CD206
OT  - Endo180
OT  - Receptor endocytosis
OT  - collagen
OT  - collectin
OT  - immune regulation
OT  - innate immunity
OT  - mannose binding lectin
OT  - mannose receptor
OT  - protein turnover
OT  - receptor structure-function
OT  - surfactant protein
COIS- Conflict of interest-The authors declare that they have no conflicts of interest 
      with the contents of this article.
EDAT- 2020/05/20 06:00
MHDA- 2021/01/12 06:00
PMCR- 2021/07/03
CRDT- 2020/05/20 06:00
PHST- 2020/04/06 00:00 [received]
PHST- 2020/05/15 00:00 [revised]
PHST- 2020/05/20 06:00 [pubmed]
PHST- 2021/01/12 06:00 [medline]
PHST- 2020/05/20 06:00 [entrez]
PHST- 2021/07/03 00:00 [pmc-release]
AID - S0021-9258(17)50336-1 [pii]
AID - RA120.013710 [pii]
AID - 10.1074/jbc.RA120.013710 [doi]
PST - ppublish
SO  - J Biol Chem. 2020 Jul 3;295(27):9157-9170. doi: 10.1074/jbc.RA120.013710. Epub 
      2020 May 18.