PMID- 22778404
OWN - NLM
STAT- MEDLINE
DCOM- 20121029
LR  - 20211203
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 109
IP  - 33
DP  - 2012 Aug 14
TI  - Sialin (SLC17A5) functions as a nitrate transporter in the plasma membrane.
PG  - 13434-9
LID - 10.1073/pnas.1116633109 [doi]
AB  - In vivo recycling of nitrate (NO(3)(-)) and nitrite (NO(2)(-)) is an important 
      alternative pathway for the generation of nitric oxide (NO) and maintenance of 
      systemic nitrate-nitrite-NO balance. More than 25% of the circulating NO(3)(-) is 
      actively removed and secreted by salivary glands. Oral commensal bacteria convert 
      salivary NO(3)(-) to NO(2)(-), which enters circulation and leads to NO 
      generation. The transporters for NO(3)(-) in salivary glands have not yet been 
      identified. Here we report that sialin (SLC17A5), mutations in which cause Salla 
      disease and infantile sialic acid storage disorder (ISSD), functions as an 
      electrogenic 2NO(3)(-)/H(+) cotransporter in the plasma membrane of salivary 
      gland acinar cells. We have identified an extracellular pH-dependent anion 
      current that is carried by NO(3)(-) or sialic acid (SA), but not by Br(-), and is 
      accompanied by intracellular acidification. Both responses were reduced by 
      knockdown of sialin expression and increased by the plasma membrane-targeted 
      sialin mutant (L22A-L23A). Fibroblasts from patients with ISSD displayed reduced 
      SA- and NO(3)(-)-induced currents compared with healthy controls. Furthermore, 
      expression of disease-associated sialin mutants in fibroblasts and salivary gland 
      cells suppressed the H(+)-dependent NO(3)(-) conductance. Importantly, 
      adenovirus-dependent expression of the sialinH183R mutant in vivo in pig salivary 
      glands decreased NO(3)(-) secretion in saliva after intake of a NO(3)(-)-rich 
      diet. Taken together, these data demonstrate that sialin mediates nitrate influx 
      into salivary gland and other cell types. We suggest that the 2NO(3)(-)/H(+) 
      transport function of sialin in salivary glands can contribute significantly to 
      clearance of serum nitrate, as well as nitrate recycling and physiological 
      nitrite-NO homeostasis.
FAU - Qin, Lizheng
AU  - Qin L
AD  - Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration 
      and Function Reconstruction, Capital Medical University School of Stomatology, 
      Beijing 100050, China.
FAU - Liu, Xibao
AU  - Liu X
FAU - Sun, Qifei
AU  - Sun Q
FAU - Fan, Zhipeng
AU  - Fan Z
FAU - Xia, Dengsheng
AU  - Xia D
FAU - Ding, Gang
AU  - Ding G
FAU - Ong, Hwei Ling
AU  - Ong HL
FAU - Adams, David
AU  - Adams D
FAU - Gahl, William A
AU  - Gahl WA
FAU - Zheng, Changyu
AU  - Zheng C
FAU - Qi, Senrong
AU  - Qi S
FAU - Jin, Luyuan
AU  - Jin L
FAU - Zhang, Chunmei
AU  - Zhang C
FAU - Gu, Liankun
AU  - Gu L
FAU - He, Junqi
AU  - He J
FAU - Deng, Dajun
AU  - Deng D
FAU - Ambudkar, Indu S
AU  - Ambudkar IS
FAU - Wang, Songlin
AU  - Wang S
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120709
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Acids)
RN  - 0 (Anion Transport Proteins)
RN  - 0 (Anions)
RN  - 0 (Nitrate Transporters)
RN  - 0 (Nitrates)
RN  - 0 (Organic Anion Transporters)
RN  - 0 (Protons)
RN  - 0 (Symporters)
RN  - 0 (sialic acid transport proteins)
RN  - GZP2782OP0 (N-Acetylneuraminic Acid)
SB  - IM
CIN - Proc Natl Acad Sci U S A. 2012 Aug 14;109(33):13144-5. PMID: 22851765
MH  - Acids/metabolism
MH  - Adenoviridae/metabolism
MH  - Animals
MH  - Anion Transport Proteins/*metabolism
MH  - Anions
MH  - Biological Transport
MH  - Cell Membrane/*metabolism
MH  - Fibroblasts/metabolism/pathology
MH  - Intracellular Space/metabolism
MH  - Mutation/genetics
MH  - N-Acetylneuraminic Acid/metabolism
MH  - Nitrate Transporters
MH  - Nitrates/metabolism
MH  - Organic Anion Transporters/genetics/*metabolism
MH  - Protons
MH  - Sialic Acid Storage Disease/metabolism
MH  - Submandibular Gland/cytology/metabolism
MH  - Sus scrofa
MH  - Symporters/genetics/*metabolism
PMC - PMC3421170
COIS- The authors declare no conflict of interest.
EDAT- 2012/07/11 06:00
MHDA- 2012/10/30 06:00
PMCR- 2013/02/14
CRDT- 2012/07/11 06:00
PHST- 2012/07/11 06:00 [entrez]
PHST- 2012/07/11 06:00 [pubmed]
PHST- 2012/10/30 06:00 [medline]
PHST- 2013/02/14 00:00 [pmc-release]
AID - 1116633109 [pii]
AID - 201116633 [pii]
AID - 10.1073/pnas.1116633109 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2012 Aug 14;109(33):13434-9. doi: 
      10.1073/pnas.1116633109. Epub 2012 Jul 9.