Table 1.
Various protein interactions and functions of APP
| Function | APP domain | Binding partners | References |
|---|---|---|---|
| Surface receptor | CAPPD | F-spondin | Ho and Sudhof (2004) |
| Aβ, undefined | ApoE | Strittmatter et al (1993) and reviewed in Turner et al (2003) | |
| Undefined | Aβ | Lorenzo et al (2000) | |
| Adhesion molecule | |||
| Cell/substratum | Undefined, Aβ | ECM (laminin, collagen, perlecan, etc.) | Kibbey et al (1993) and reviewed in Small et al (1999) and Turner et al (2003) |
| E1 (GFLD) | Fibulin-1 | Ohsawa et al (2001) | |
| E1, E2 (HBD 1+2) | HSPG | Reviewed in Small et al (1999) | |
| AICD | Fe65, Menaa | Sabo et al (2001) | |
| Cell/cell | CAPPD | CAPPD (in cis or trans?) | Wang and Ha (2004) |
| E1 | E1 (in cis or trans?) | Soba et al (2005) | |
| Regulator of neuronal processes | |||
| Neurite outgrowth | sAPP | Undefined | Reviewed in Mattson (1997) and Small et al (1999) |
| Aβ | Undefined | Reviewed in Mattson (1997) and Small et al (1999) | |
| Dendritic arborization | CAPPD | Undefined | Reviewed in Mattson (1997) and De Strooper and Annaert (2000) |
| AICD (C99) | Abl, profilin, JIP | Leyssen et al (2005) | |
| Synaptogenesis | sAPP | Undefined | Reviewed in Mattson (1997) and Small et al (1999) |
| Undefined, AICD | Fasciclin II, X11/Mint | Ashley et al (2005) | |
| Synaptic plasticity | sAPP | Undefined | Reviewed in Mattson (1997) and Turner et al (2003) |
| Neuronal excitability | sAPP | Undefined | Reviewed in Mattson (1997) and Turner et al (2003) |
| Axonal transport cargo receptor | AICD | JIP, kinesina | Kamal et al (2000, 2001), Taru et al (2002), Matsuda et al (2003) and Lazarov et al (2005) |
| Regulator of neuronal stem cell division | sAPP | Undefined (present on type-A and type-C cells in SVZ) | Caille et al (2004) |
| Signaling molecule | |||
| G-protein-coupled receptor protein signaling pathway | AICD | G(o) | Nishimoto et al (1993) |
| Kinase-mediated signaling cascades | AICD | Abl, Shc/Grb2, JIP, Dab | Russo et al (2002), Tarr et al (2002) and reviewed in Koo (2002) and King and Scott Turner (2004) |
| sAPP | Undefined | Reviewed in Mattson (1997) | |
| Gene transcription | AICD (C59, C57, C49) | Fe65, Fe65L, JIP, Mint/X11, Numb | Roncarati et al (2002), Scheinfeld et al (2003), Merdes et al (2004) and reviewed in Mattson (1997), Koo (2002), Turner et al (2003), Beglopoulos et al (2004) |
| Regulator of calcium homeostasis | Aβ, undefined | Undefined | Reviewed in LaFerla (2002), Abramov et al (2004) |
| AICD (C99, C57) | Undefined (via phosphoinositide) | Leissring et al (2002) | |
| Regulator of metal homeostasis | CuBD | Cu2+ | Reviewed in Maynard et al (2005) |
| Regulator of cell survival/death | |||
| Neurotrophic | sAPP | Undefined | Reviewed in Mattson (1997) |
| Neurotoxic | Aβb | Undefined, APP | Lu et al (2003) and reviewed in Mattson (1997), Walsh and Selkoe (2004) |
| AICD casp (C31) | Caspases, APP-BP1 | Chow et al (1996) and reviewed in Milligan (2000) | |
| AICD (C59, C57) | Undefined (signals through GSK3β, Tip60) | Kinoshita et al (2002a) and Kim et al (2003) | |
| |
AICD (a.a. 649–664) |
Undefined |
Bertrand et al (2001) |
| ECM=extracellular matrix; HBD=heparin-binding domain; HSPG=heparan sulfate proteoglycans; SVZ=subventricular zone. | |||
| The different suggested biological functions of APP are summarized. The proteins identified to interact with APP and relevant for the described functions are mentioned, together with further references. | |||
| aIndirect interaction. | |||
| bOligomer versus monomer? | |||