STE20/SPS1-related proline/alanine-rich kinase (SPAK) is critical for sodium reabsorption in isolated, perfused thick ascending limb

Chih-Jen Cheng; Joonho Yoon; Michel Baum; Chou-Long Huang

doi:10.1152/ajprenal.00493.2013

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STE20/SPS1-related proline/alanine-rich kinase (SPAK) is critical for sodium reabsorption in isolated, perfused thick ascending limb

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STE20/SPS1-related proline/alanine-rich kinase (SPAK) is critical for sodium reabsorption in isolated, perfused thick ascending limb

Chih-Jen Cheng, Joonho Yoon, Michel Baum and Chou-Long Huang

American journal of physiology. Renal physiology, Vol.308(5), pp.F437-F443

03/01/2015

DOI: 10.1152/ajprenal.00493.2013

PMCID: PMC4346744

PMID: 25477470

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Abstract

SPAK [STE20 (sterile 20)/SPS1-related proline/alanine-rich kinase] kinase consists of a full-length (FL-) and an alternatively spliced kidney-specific (KS-) isoform. SPAK regulates the NaCl cotransporter (NCC) in the distal convoluted tubule (DCT). The relative abundance and role of FL- vs. KS-SPAK in regulating Na(+)-K(+)-2Cl(-) cotransporter (NKCC2) in thick ascending limb (TAL) are not completely understood. Here, we report that FL-SPAK mRNA was the most abundant in medullary TAL (mTAL), followed by cortical TAL (cTAL) and DCT. KS-SPAK mRNA abundance was relatively lower than FL-SPAK. The ratios of FL-SPAK to KS-SPAK in mTAL, cTAL, and DCT were 12.3, 12.5, and 10.2, respectively. To examine the role of SPAK in the regulation of sodium transport in TAL, we used in vitro microperfusion of mTAL and cTAL isolated from wild-type (WT) and SPAK knockout mice (SPAK-KO) that lack both FL- and KS-SPAK. The rates of sodium absorption in cTAL and mTAL of SPAK-KO mice were 34.5 and 12.5% of WT tubules, respectively. The mRNA levels of related OSR1 kinase and SPAK protease Dnpep in SPAK-KO tubules were not significantly different from WT tubules. We next examined the role of SPAK in the regulation of sodium reabsorption by vasopressin in TAL. Vasopressin increased sodium reabsorption by ∼80% in both mTAL and cTAL from WT mice. While baseline sodium reabsorption was lower in SPAK-KO tubules, vasopressin increased sodium reabsorption over twofold. In conclusion, the combined net effect of SPAK isoforms on sodium reabsorption in TAL is stimulatory. SPAK is not essential for vasopressin stimulation of sodium reabsorption in TAL.

Renal Reabsorption

Solute Carrier Family 12, Member 1 - metabolism

Animals

Protein Isoforms - metabolism

Mice, Inbred C57BL

Glutamyl Aminopeptidase - metabolism

Loop of Henle - metabolism

Sodium - metabolism

In Vitro Techniques

Protein-Serine-Threonine Kinases - metabolism

Mice, Knockout

Vasopressins

Details

Title: Subtitle: STE20/SPS1-related proline/alanine-rich kinase (SPAK) is critical for sodium reabsorption in isolated, perfused thick ascending limb
Creators: Chih-Jen Cheng - Department of Medicine, Division of Nephrology, UT Southwestern Medical Center, Dallas, Texas; Department of Medicine, Division of Nephrology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan laurence1234kimo@yahoo.com.tw
Joonho Yoon - Department of Medicine, Division of Nephrology, UT Southwestern Medical Center, Dallas, Texas
Michel Baum - Department of Medicine, Division of Nephrology, UT Southwestern Medical Center, Dallas, Texas; Department of Pediatrics, UT Southwestern Medical Center, Dallas, Texas; and
Chou-Long Huang - Department of Medicine, Division of Nephrology, UT Southwestern Medical Center, Dallas, Texas
Resource Type: Journal article
Publication Details: American journal of physiology. Renal physiology, Vol.308(5), pp.F437-F443
DOI: 10.1152/ajprenal.00493.2013
PMID: 25477470
PMCID: PMC4346744
NLM abbreviation: Am J Physiol Renal Physiol
ISSN: 0363-6127
eISSN: 1522-1466
Grant note: DK079328 / NIDDK NIH HHS DK59530 / NIDDK NIH HHS DK41612 / NIDDK NIH HHS
Language: English
Date published: 03/01/2015
Academic Unit: Nephrology; Internal Medicine
Record Identifier: 9984094769002771

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