Liver-specific ZP domain-containing protein (LZP) as a new partner of Tamm-Horsfall protein harbors on renal tubules.
Liver-specific ZP domain-containing protein (LZP) was recently identified as a secreted protein that is specifically expressed in liver. However, the physiological effects of LZP are largely unknown. In this study, we found that LZP was detectable in mouse kidneys, testes, ovaries and heart, in addition to liver. LZP was localized in the spermatid cells of testes, corpus luteum cells of ovaries, and cardiac muscle cells of heart. But the protein mainly anchored on the apical membrane of the thick ascending limb of the loop of Henle (TAL) cell in mouse kidney. In rat kidney LZP and Tamm-Horsfall protein (THP) were co-localized in TAL. The in vivo interaction between LZP and THP was confirmed in kidney and urine by co-immunoprecipitation assay, and the in vitro interaction was detected by GST pull-down assay, implying that the interaction could be independent on N-linked glycosylated modification of LZP. Surprisingly, LZPs with intramolecular disulfide bridges could self-interact, and then self-aggregate into spheres of varying sizes, but not polymerize into filaments. The finding that LZP might act as a new partner of THP would provide novel insights into renal functions related to THP and LZP, such as the urothelial permeability barrier and the host defense against the adhesion of pathogens.
Shen
Hai-Lian
HL
Shanghai-Ministry Key Laboratory of Disease and Health Genomics, Chinese National Human Genome Center, Shanghai, China.
Xu
Zhi-Gang
ZG
Huang
Li-Yu
LY
Liu
Dong
D
Lin
Dao-Hong
DH
Cao
Jia-Bin
JB
Zhang
Xin
X
Wang
Zhi-Qin
ZQ
Wang
Wen-Hui
WH
Yang
Peng-Yuan
PY
Han
Ze-Guang
ZG
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009088:Mucoproteins / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D058949:Uromodulin
C492692:LZP protein, mouse; D008565:Membrane Proteins; D009088:Mucoproteins; C477697:OIT3 protein, human; C492693:Oit3 protein, rat; D011993:Recombinant Fusion Proteins; C548612:UMOD protein, human; C548613:Umod protein, mouse; C548614:Umod protein, rat; D058949:Uromodulin