Functional requirement of aquaporin-5 in plasma membranes of sweat glands.
The distribution and function of aquaporins (AQPs) have not previously been defined in sweat glands. In this study, AQP1, AQP3, and AQP5 mRNA were demonstrated in rat paw by reverse transcription (RT)-PCR, but AQP2 and AQP4 were not. AQP1, AQP3, and AQP5 protein were confirmed in these tissues by immunoblotting. AQP1 was identified in capillary endothelial cells by immunohistochemical labeling, but not in sweat glands or epidermis. Abundant AQP3 expression was seen in basal levels of epidermis, but not in sweat glands. AQP2 and AQP4 were not observed in either skin or sweat glands. Immunohistochemical labeling revealed abundant AQP5 in secretory parts of rat and mouse sweat glands, where immunoelectron microscopy demonstrated abundant AQP5 labeling in the apical plasma membrane. AQP5 immunolabeling of human sweat glands yielded a similar pattern. To establish the role of AQP5 in sweat secretion, we tested the response of adult mice to s.c. injection of pilocarpine, as visualized by reaction of secreted amylase with iodine/starch. The number of active sweat glands was dramatically reduced in AQP5-null (-/-) mice compared with heterozygous (+/-) and wild-type (+/+) mice. We conclude that the presence of AQP5 in plasma membranes of sweat glands is essential for secretion, providing potential insight into mechanisms underlying mammalian thermoregulation, tactile sensitivity, and the pathophysiology of hyperhidrosis.
Nejsum
Lene N
LN
The Water and Salt Research Center and the Department of Human Genetics, University of Aarhus, DK-8000 Aarhus, Denmark.
Kwon
Tae-Hwan
TH
Jensen
Uffe B
UB
Fumagalli
Ornella
O
Frøkiaer
Jørgen
J
Krane
Carissa M
CM
Menon
Anil G
AG
King
Landon S
LS
Agre
Peter C
PC
Nielsen
Søren
S
D000818:Animals; D051399:Aquaporin 2; D051400:Aquaporin 3; D051401:Aquaporin 4; D051402:Aquaporin 5; D051403:Aquaporin 6; D020346:Aquaporins / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism*; D006579:Heterozygote; D015151:Immunoblotting; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D016253:Microscopy, Immunoelectron; D018721:Muscarinic Agonists / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism; D013347:Subcellular Fractions; D013545:Sweat Glands / Q000378:metabolism*; D014867:Water / Q000737:chemistry
C496024:Aqp2 protein, mouse; C496025:Aqp2 protein, rat; C496028:Aqp3 protein, mouse; C496029:Aqp3 protein, rat; C496031:Aqp4 protein, mouse; C496032:Aqp4 protein, rat; C496038:Aqp5 protein, mouse; C496040:Aqp5 protein, rat; D051399:Aquaporin 2; D051401:Aquaporin 4; D051402:Aquaporin 5; D051403:Aquaporin 6; D020346:Aquaporins; D008565:Membrane Proteins; D018721:Muscarinic Agonists; D012333:RNA, Messenger; D010862:Pilocarpine; D014867:Water; D051400:Aquaporin 3