The Proline Rich Domain (PRD) of dynamin binds to SH3 domains of many proteins, and we believe that these interactions recruit dynamin to its many sites of action in the cell. In dynamin I there are 36 prolines in 110 amino acids. One of the strongest interactions is with amphiphysin which is itself a dimer, and binds to clathrin, AP2 adaptors and membranes. Thus this protein would be predicted to effectively recruit dynamin to clathrin-coated pits on the plasma membrane. Of course there must be other recruitment proteins for other compartments and for other budding events, and the following proteins have all been linked to dynamin function by virtue of binding the PRD:
Amphiphysin is the major dynamin binding partner in brain extracts and thus there is a separate link giving details of this protein (Amphiphysin).
List of some other interacting proteins in alphabetical order
Actin binding protein1 (Abp1/SH3P7/HIP55) (Kessels et al 2001 J Cell Biol, Mise-Omata et al 22003 BBRC) Overexpression of the SH3 domain of this F-actin binding protein inhibits transferrin endocytosis, but overexpression of the actin binding module does not interfere. RNAi also inhibits transferrin endocytosis.
Calcineurin (Lai et al 1999 J Biol Chem) The interaction with dynamin1 is calcium dependent with an EC50 in the range of 0.1-0.4microM.
Cortactin (McNiven et al 2000 J Cell Biol) The chromosome region covering cortactin (EMS1) is amplified in several human cancers including those of the breast head and neck. Overexpression of cortactin increases cell motility and thus may enhance the invasion/metastatic spread of cancers. The link between endocytosis (dynamin binding), actin bundling and motility may well be key to this whole process.
EEN (Extra eleven-nineteen leukemia fusion gene) (So et al 2000 Leukemia) has an N-terminal SH3 domain that binds to dynamin. EEN is a fusion partner for the mixed lineage leukaemia gene, MLL (also called HRX, ALL-1). In acute leukaemias MLL has been found fused to at least 16 different proteins.
Endophilin (Ringstad et al 1997 PNAS) The N-terminal BAR-domain of this protein bindings and tubulates liposomes, while the C-terminal SH3 domain binds to both synaptojanin and dynamin. The Drosophila endophilin A is essential and mutants with reduced levels of protein show severe defects in synaptic vesicle endocytosis (Guichet et al 2002 EMBO J, Verstreken et al 2002 Cell). The protein is proposed to have a lysophosphatydic acid transferase activity which would aid the budding of vesicles (Schmidt et al 1999 Nature), but this activity is not essential for in vitro membrane tubulation (Farsad et al 2001 J Cell Biol.).
Grb2 binds tightly to dynamin and can stimulate dynamin oligomerisation by virtue of its 2 SH3 domains (N-SH3 and C-SH3). Thus this protein could well be important in dynamin recruitment, but the implication that the PRD binding by an SH3 domain may stimulate GTP hydrolysis is likely indirectly due to its effect on stimulating oligomerisation (Wigge et al 1997 Current Biol) (see also Gout et al 1993, Miki et al 1994 J Biol Chem, Seedorf et al 1994 J Biol Chem). Grb2 is important in the internalisation of EGF receptors via macropinocytic structures rather than clathrin-coated vesicles (Yamazaki et al 2002). This process is dynamin dependent.
Intersectin/Dap160/Ese/SH3P17/SH3P18 (Roos and Kelly 1998 JBC, Yamabhai et al 1998 JBC, Okamoto et al 1999 JBC, Sengar et al 1999 EMBO J 1999) This protein has 2 N-terminal EH domains that can bind epsins, four (Drosophila Dap160) or five (mammalian intersectin/Ese) SH3 domains that bind dynamins and other proteins with Proline rich motifs. It is suggested to be a scaffolding protein helping to anchor endocytic proteins together at endocytic zones. Unlike Drosophila amphiphysin, Drosophila Dap160 (Dynamin-associated-protein of 160kDa) interacts with Drosophila dynamin. Ese1 stands for EH domain and SH3 domain regulator of endocytosis.
Mixed-lineage kinase 2 (MLK2) (Rasmussen et al 1998 BJ) A protein kinase expressed at high levels in the brain that binds to dynamin via its SH3 domain.
NCK (Wunderlich et al 1999 Cell Signal) Nck is an adaptor molecule (like Grb2) with an SH2 domain and three SH3 domains. These adaptors are thought to link receptor tyrosine kinases to signalling pathways. The third SH3 domain of Nck interacts with both Sos (a guanine nucleotide exchange protein) and dynamin.
Pacsin/Syndapin/Focal Adhesion Protein 52 (FAP52) (Modregger et al 2000 J Cell Sci, Qualmann and Kelly 2000 J Cell Biol) Binds to N-WASP and promotes actin polymerisation involving the Arp2/3 complex.Pacsin: protein kinase C and casein kinase substrate in neurons.
P85-PI3Kinase (Gout et al 1993 Cell)
Phopholipase Cg (PLCg) (Seedorf et al 1994 JBC) The SH3 domain binds dynamin.
Profilin (Witke et al 1998 EMBO J) A nucleotide exchange factor for monomeric actin that binds to dynamin.
Shank/ProSAP (Okamoto et al 2001 J Biol Chem) These are postsynaptic density scaffolding proteins that interact specifically with dynamin2. While the interaction is with the PRD of dynamin2 it does not involve an SH3 domain.
Src (Foster-Barber and Bishop 1998 PNAS) The SH3 domain of this non-receptor tyrosine kinase binds to dynamin. Phosphorylation of dynamin by Src regulates its self-assembly and ligand-induced endocytosis of the EGF receptor (Ahn et al 2002 J Biol Chem).
Auxilin and Hsc70 have also been proposed to interact with dynamin via the GTPase or GED domains (Newmyer et al 2003 Dev. Cell)
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(Please let us know of other proteins that should be included with a reference
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