Calsenilin Explained

Calsenilin is a protein that in humans is encoded by the KCNIP3 gene.^{[1] [2] [3]}

Function

This gene encodes a member of the family of voltage-gated potassium (Kv) channel-interacting proteins, which belong to the neuronal calcium sensor family of proteins.^{[4] [5]} Members of this family are small calcium binding proteins containing EF-hand-like domains. They are integral subunit components of native Kv4 channel complexes that may regulate A-type currents, and hence neuronal excitability, in response to changes in intracellular calcium. The encoded protein also functions as a calcium-regulated transcriptional repressor, and interacts with presenilins. In addition, the protein has been shown to transcriptionally repress A20 (TNFAIP3) expression and thus modulate the anti-inflammatory signaling.^[6] Alternatively spliced transcript variants encoding different isoforms have been described.

Interactions

Calsenilin has been shown to interact with PSEN1^[7] and PSEN2.^{[1] [8]}

See also

• Voltage-gated potassium channel

Further reading

• Carrión AM, Mellström B, Naranjo JR . Protein Kinase A-Dependent Derepression of the Human Prodynorphin Gene via Differential Binding to an Intragenic Silencer Element . Mol. Cell. Biol. . 18 . 12 . 6921–9 . 1998 . 9819380 . 109275 . 10.1128/MCB.18.12.6921.
• An WF, Bowlby MR, Betty M, Cao J, Ling HP, Mendoza G, Hinson JW, Mattsson KI, Strassle BW, Trimmer JS, Rhodes KJ . Modulation of A-type potassium channels by a family of calcium sensors . Nature . 403 . 6769 . 553–6 . 2000 . 10676964 . 10.1038/35000592 . 2000Natur.403..553A . 4419472 .
• Leissring MA, Yamasaki TR, Wasco W, Buxbaum JD, Parker I, LaFerla FM . Calsenilin reverses presenilin-mediated enhancement of calcium signaling . Proc. Natl. Acad. Sci. U.S.A. . 97 . 15 . 8590–3 . 2000 . 10900016 . 26992 . 10.1073/pnas.97.15.8590 . 2000PNAS...97.8590L . free .
• Buxbaum JD, Lilliehook C, Chan JY, Go RC, Bassett SS, Tanzi RE, Wasco W, Blacker D . Genomic structure, expression pattern, and chromosomal localization of the human calsenilin gene: no association between an exonic polymorphism and Alzheimer's disease . Neurosci. Lett. . 294 . 3 . 135–8 . 2000 . 11072133 . 10.1016/S0304-3940(00)01553-6 . 16765518 .
• Ledo F, Carrión AM, Link WA, Mellström B, Naranjo JR . DREAM-αCREM Interaction via Leucine-Charged Domains Derepresses Downstream Regulatory Element-Dependent Transcription . Mol. Cell. Biol. . 20 . 24 . 9120–6 . 2001 . 11094064 . 102170 . 10.1128/MCB.20.24.9120-9126.2000 .
• Jo DG, Kim MJ, Choi YH, Kim IK, Song YH, Woo HN, Chung CW, Jung YK . Pro-apoptotic function of calsenilin/DREAM/KChIP3 . FASEB J. . 15 . 3 . 589–91 . 2001 . 11259376 . 10.1096/fj.00-0541fje . 37815129 . free .
• Choi EK, Zaidi NF, Miller JS, Crowley AC, Merriam DE, Lilliehook C, Buxbaum JD, Wasco W . Calsenilin is a substrate for caspase-3 that preferentially interacts with the familial Alzheimer's disease-associated C-terminal fragment of presenilin 2 . J. Biol. Chem. . 276 . 22 . 19197–204 . 2001 . 11278424 . 10.1074/jbc.M008597200 . free .
• Osawa M, Tong KI, Lilliehook C, Wasco W, Buxbaum JD, Cheng HY, Penninger JM, Ikura M, Ames JB . Calcium-regulated DNA binding and oligomerization of the neuronal calcium-sensing protein, calsenilin/DREAM/KChIP3 . J. Biol. Chem. . 276 . 44 . 41005–13 . 2001 . 11535596 . 10.1074/jbc.M105842200 . free .
• Cheng HY, Pitcher GM, Laviolette SR, Whishaw IQ, Tong KI, Kockeritz LK, Wada T, Joza NA, Crackower M, Goncalves J, Sarosi I, Woodgett JR, Oliveira-dos-Santos AJ, Ikura M, van der Kooy D, Salter MW, Penninger JM . DREAM is a critical transcriptional repressor for pain modulation . Cell . 108 . 1 . 31–43 . 2002 . 11792319 . 10.1016/S0092-8674(01)00629-8 . 16602843 . free .
• Lilliehook C, Chan S, Choi EK, Zaidi NF, Wasco W, Mattson MP, Buxbaum JD . Calsenilin enhances apoptosis by altering endoplasmic reticulum calcium signaling . Mol. Cell. Neurosci. . 19 . 4 . 552–9 . 2002 . 11988022 . 10.1006/mcne.2001.1096 . 42446025 .
• Takimoto K, Yang EK, Conforti L . Palmitoylation of KChIP splicing variants is required for efficient cell surface expression of Kv4.3 channels . J. Biol. Chem. . 277 . 30 . 26904–11 . 2002 . 12006572 . 10.1074/jbc.M203651200 . free .
• Ledo F, Kremer L, Mellström B, Naranjo JR . Ca2+-dependent block of CREB–CBP transcription by repressor DREAM . EMBO J. . 21 . 17 . 4583–92 . 2002 . 12198160 . 126180 . 10.1093/emboj/cdf440 .
• Zaidi NF, Berezovska O, Choi EK, Miller JS, Chan H, Lilliehook C, Hyman BT, Buxbaum JD, Wasco W . Biochemical and immunocytochemical characterization of calsenilin in mouse brain . Neuroscience . 114 . 1 . 247–63 . 2002 . 12207970 . 10.1016/S0306-4522(02)00251-8 . 12738777 .
• Sanz C, Horita M, Fernandez-Luna JL . Fas signaling and blockade of Bcr-Abl kinase induce apoptotic Hrk protein via DREAM inhibition in human leukemia cells . Haematologica . 87 . 9 . 903–7 . 2004 . 12217801 .
• Schrader LA, Anderson AE, Mayne A, Pfaffinger PJ, Sweatt JD . PKA modulation of Kv4.2-encoded A-type potassium channels requires formation of a supramolecular complex . J. Neurosci. . 22 . 23 . 10123–33 . 2002 . 12451113 . 6758737 . 10.1523/JNEUROSCI.22-23-10123.2002.
• Hong YM, Jo DG, Lee MC, Kim SY, Jung YK . Reduced expression of calsenilin/DREAM/KChIP3 in the brains of kainic acid-induced seizure and epilepsy patients . Neurosci. Lett. . 340 . 1 . 33–6 . 2003 . 12648752 . 10.1016/S0304-3940(03)00067-3 . 10647796 .
• Shibata R, Misonou H, Campomanes CR, Anderson AE, Schrader LA, Doliveira LC, Carroll KI, Sweatt JD, Rhodes KJ, Trimmer JS . A fundamental role for KChIPs in determining the molecular properties and trafficking of Kv4.2 potassium channels . J. Biol. Chem. . 278 . 38 . 36445–54 . 2003 . 12829703 . 10.1074/jbc.M306142200 . free .
• Venn N, Haynes LP, Burgoyne RD . Specific effects of KChIP3/calsenilin/DREAM, but not KChIPs 1, 2 and 4, on calcium signalling and regulated secretion in PC12 cells . Biochem. J. . 413 . 1 . 71–80 . 2008 . 18393943 . 2474559 . 10.1042/BJ20080441 .

External links

• • NCS proteins

Notes and References

1. Buxbaum JD, Choi EK, Luo Y, Lilliehook C, Crowley AC, Merriam DE, Wasco W . Calsenilin: a calcium-binding protein that interacts with the presenilins and regulates the levels of a presenilin fragment . Nat Med . 4 . 10 . 1177–81 . October 1998 . 9771752 . 10.1038/2673 . 10799492 .
2. Carrión AM, Link WA, Ledo F, Mellström B, Naranjo JR . DREAM is a Ca2+-regulated transcriptional repressor . Nature . 398 . 6722 . 80–4 . March 1999 . 10078534 . 10.1038/18044 . 1999Natur.398...80C . 204991618 .
3. Web site: Entrez Gene: KCNIP3 Kv channel interacting protein 3, calsenilin.
4. Burgoyne RD . Neuronal Calcium Sensor Proteins: Generating Diversity in Neuronal Ca2+ Signalling . Nat. Rev. Neurosci. . 8 . 3 . 182–193 . 2007 . 17311005 . 1887812 . 10.1038/nrn2093 .
5. Burgoyne RD, O'Callaghan DW, Hasdemir B, Haynes LP, Tepikin AV . Neuronal Ca2+-sensor proteins: multitalented regulators of neuronal function . Trends Neurosci. . 27 . 4 . 203–9 . 2004 . 15046879 . 10.1016/j.tins.2004.01.010 . 24156457 .
6. Tiruppathi C,Soni D, Wang DM, et al. . The transcription factor DREAM represses A20 and mediates inflammation . Nat Immunol . 15 . 3 . 239–247 . March 2014 . 24487321 . 4005385 . 10.1038/ni.2823 .
7. Kashiwa A, Yoshida H, Lee S, Paladino T, Liu Y, Chen Q, Dargusch R, Schubert D, Kimura H . Isolation and characterization of novel presenilin binding protein . J. Neurochem. . 75 . 1 . 109–16 . July 2000 . 10854253 . 10.1046/j.1471-4159.2000.0750109.x . 24838995 . free .
8. Choi EK, Zaidi NF, Miller JS, Crowley AC, Merriam DE, Lilliehook C, Buxbaum JD, Wasco W . Calsenilin is a substrate for caspase-3 that preferentially interacts with the familial Alzheimer's disease-associated C-terminal fragment of presenilin 2 . J. Biol. Chem. . 276 . 22 . 19197–204 . June 2001 . 11278424 . 10.1074/jbc.M008597200 . free .