APLP1 explained

Amyloid precursor like protein 1, also known as APLP1, is a protein encoded by the APLP1 gene in humans.^{[1] [2]} APLP1 along with APLP2 are important modulators of glucose and insulin homeostasis.

Function

This gene encodes a member of the highly conserved amyloid precursor protein gene family. The encoded protein is a membrane-associated glycoprotein that is cleaved by secretases in a manner similar to amyloid beta A4 precursor protein cleavage. This cleavage liberates an intracellular cytoplasmic fragment that may act as a transcriptional activator. The encoded protein may also play a role in synaptic maturation during cortical development. Alternatively spliced transcript variants encoding different isoforms have been described.^[3]

APLP1 and APLP2 double knockout mice display hypoglycemia and hyperinsulinemia indicating that these two proteins are important modulators of glucose and insulin homeostasis.^[4]

APLP1 has also been implicated in the transmission pathologic α-synuclein in Parkinson's disease^{[5] [6]}

References

Further reading

• Bayer TA, Cappai R, Masters CL, Beyreuther K, Multhaup G . It all sticks together--the APP-related family of proteins and Alzheimer's disease . Molecular Psychiatry . 4 . 6 . 524–528 . November 1999 . 10578233 . 10.1038/sj.mp.4000552 . free .
• Kim TW, Wu K, Xu JL, McAuliffe G, Tanzi RE, Wasco W, Black IB . Selective localization of amyloid precursor-like protein 1 in the cerebral cortex postsynaptic density . Brain Research. Molecular Brain Research . 32 . 1 . 36–44 . August 1995 . 7494461 . 10.1016/0169-328X(95)00328-P .
• Bush AI, Pettingell WH, de Paradis M, Tanzi RE, Wasco W . The amyloid beta-protein precursor and its mammalian homologues. Evidence for a zinc-modulated heparin-binding superfamily . The Journal of Biological Chemistry . 269 . 43 . 26618–26621 . October 1994 . 7929392 . 10.1016/S0021-9258(18)47062-7 . free .
• Wasco W, Brook JD, Tanzi RE . The amyloid precursor-like protein (APLP) gene maps to the long arm of human chromosome 19 . Genomics . 15 . 1 . 237–239 . January 1993 . 8432545 . 10.1006/geno.1993.1047 .
• Bressler SL, Gray MD, Sopher BL, Hu Q, Hearn MG, Pham DG, Dinulos MB, Fukuchi K, Sisodia SS, Miller MA, Disteche CM, Martin GM . cDNA cloning and chromosome mapping of the human Fe65 gene: interaction of the conserved cytoplasmic domains of the human beta-amyloid precursor protein and its homologues with the mouse Fe65 protein . Human Molecular Genetics . 5 . 10 . 1589–1598 . October 1996 . 8894693 . 10.1093/hmg/5.10.1589 . free .
• Paliga K, Peraus G, Kreger S, Dürrwang U, Hesse L, Multhaup G, Masters CL, Beyreuther K, Weidemann A . Human amyloid precursor-like protein 1--cDNA cloning, ectopic expression in COS-7 cells and identification of soluble forms in the cerebrospinal fluid . European Journal of Biochemistry . 250 . 2 . 354–363 . December 1997 . 9428684 . 10.1111/j.1432-1033.1997.0354a.x . free .
• Lenkkeri U, Kestilä M, Lamerdin J, McCready P, Adamson A, Olsen A, Tryggvason K . Structure of the human amyloid-precursor-like protein gene APLP1 at 19q13.1 . Human Genetics . 102 . 2 . 192–196 . February 1998 . 9521588 . 10.1007/s004390050676 . 709094 .
• McNamara MJ, Ruff CT, Wasco W, Tanzi RE, Thinakaran G, Hyman BT . Immunohistochemical and in situ analysis of amyloid precursor-like protein-1 and amyloid precursor-like protein-2 expression in Alzheimer disease and aged control brains . Brain Research . 804 . 1 . 45–51 . August 1998 . 9729270 . 10.1016/S0006-8993(98)00653-2 . 25127562 . free .
• Tomita S, Ozaki T, Taru H, Oguchi S, Takeda S, Yagi Y, Sakiyama S, Kirino Y, Suzuki T . Interaction of a neuron-specific protein containing PDZ domains with Alzheimer's amyloid precursor protein . The Journal of Biological Chemistry . 274 . 4 . 2243–2254 . January 1999 . 9890987 . 10.1074/jbc.274.4.2243 . free .
• Homayouni R, Rice DS, Sheldon M, Curran T . Disabled-1 binds to the cytoplasmic domain of amyloid precursor-like protein 1 . The Journal of Neuroscience . 19 . 17 . 7507–7515 . September 1999 . 10460257 . 6782519 . 10.1523/JNEUROSCI.19-17-07507.1999 .
• Simons A, Ruppert T, Schmidt C, Schlicksupp A, Pipkorn R, Reed J, Masters CL, White AR, Cappai R, Beyreuther K, Bayer TA, Multhaup G . Evidence for a copper-binding superfamily of the amyloid precursor protein . Biochemistry . 41 . 30 . 9310–9320 . July 2002 . 12135352 . 10.1021/bi0258647 .
• Scheinfeld MH, Ghersi E, Laky K . Processing of beta-amyloid precursor-like protein-1 and -2 by gamma-secretase regulates transcription. . J. Biol. Chem. . 277 . 46 . 44195–201 . 2003 . 12228233 . 10.1074/jbc.M208110200 . etal. free .
• Walsh DM, Fadeeva JV, LaVoie MJ, Paliga K, Eggert S, Kimberly WT, Wasco W, Selkoe DJ . gamma-Secretase cleavage and binding to FE65 regulate the nuclear translocation of the intracellular C-terminal domain (ICD) of the APP family of proteins . Biochemistry . 42 . 22 . 6664–6673 . June 2003 . 12779321 . 10.1021/bi027375c .
• Yamakami M, Yoshimori T, Yokosawa H . Tom1, a VHS domain-containing protein, interacts with tollip, ubiquitin, and clathrin . The Journal of Biological Chemistry . 278 . 52 . 52865–52872 . December 2003 . 14563850 . 10.1074/jbc.M306740200 . free .
• Adlerz L, Beckman M, Holback S, Tehranian R, Cortés Toro V, Iverfeldt K . Accumulation of the amyloid precursor-like protein APLP2 and reduction of APLP1 in retinoic acid-differentiated human neuroblastoma cells upon curcumin-induced neurite retraction . Brain Research. Molecular Brain Research . 119 . 1 . 62–72 . November 2003 . 14597230 . 10.1016/j.molbrainres.2003.08.014 .
• Li Q, Südhof TC . Cleavage of amyloid-beta precursor protein and amyloid-beta precursor-like protein by BACE 1 . The Journal of Biological Chemistry . 279 . 11 . 10542–10550 . March 2004 . 14699153 . 10.1074/jbc.M310001200 . free .
• Eggert S, Paliga K, Soba P, Evin G, Masters CL, Weidemann A, Beyreuther K . The proteolytic processing of the amyloid precursor protein gene family members APLP-1 and APLP-2 involves alpha-, beta-, gamma-, and epsilon-like cleavages: modulation of APLP-1 processing by n-glycosylation . The Journal of Biological Chemistry . 279 . 18 . 18146–18156 . April 2004 . 14970212 . 10.1074/jbc.M311601200 . free .

Notes and References

1. Web site: Entrez Gene: APLP1 amyloid beta (A4) precursor-like protein 1.
2. Wasco W, Brook JD, Tanzi RE . The amyloid precursor-like protein (APLP) gene maps to the long arm of human chromosome 19 . Genomics . 15 . 1 . 237–9 . January 1993 . 8432545 . 10.1006/geno.1993.1047 .
3. Web site: Entrez Gene: APLP1 amyloid beta (A4) precursor-like protein 1.
4. Needham BE, Wlodek ME, Ciccotosto GD, Fam BC, Masters CL, Proietto J, Andrikopoulos S, Cappai R . Identification of the Alzheimer's disease amyloid precursor protein (APP) and its homologue APLP2 as essential modulators of glucose and insulin homeostasis and growth . J. Pathol. . 215 . 2 . 155–63 . June 2008 . 18393365 . 10.1002/path.2343 . 1064378 .
5. Mao X, Gu H, Kim D, Kimura Y, Wang N, Xu E, Kumbhar R, Ming X, Wang H, Chen C, Zhang S, Jia C, Liu Y, Bian H, Karuppagounder SS, Akkentli F, Chen Q, Jia L, Hwang H, Lee SH, Ke X, Chang M, Li A, Yang J, Rastegar C, Sriparna M, Ge P, Brahmachari S, Kim S, Zhang S, Shimoda Y, Saar M, Liu H, Kweon SH, Ying M, Workman CJ, Vignali DA, Muller UC, Liu C, Ko HS, Dawson VL, Dawson TM . Aplp1 interacts with Lag3 to facilitate transmission of pathologic α-synuclein . Nature Communications . 15 . 1 . 4663 . May 2024 . 38821932 . 11143359 . 10.1038/s41467-024-49016-3 .
6. Web site: 17 June 2024 . New Study Suggests Cancer Drug Could Be Used to Target Protein Connection That Spurs Parkinson’s Disease . Johns Hopkins Medicine.