A unique residue in rab3c determines the interaction with novel binding protein Zwint-1.
Exocytic events are tightly regulated cellular processes in which rab GTPases and their interacting proteins perform an important function. We set out to identify new binding partners of rab3, which mediates regulated secretion events in specialized cells. We discovered Zwint-1 as a rab3 specific binding protein that bound preferentially to rab3c. The interaction depends on a critical residue in rab3c that determines the binding efficiency of Zwint-1, which is immaterial for interaction with rabphilin3a. Rab3c and Zwint-1 are expressed highly in brain and colocalized extensively in primary hippocampal neurons. We also found that SNAP25 bound to the same region in Zwint-1 as rab3c, suggesting a new role for the kinetochore protein Zwint-1 in presynaptic events that are regulated by rab3 and SNAP25.
van Vlijmen
Thijs
T
Department of Cell Biology, University Medical Center Utrecht, Utrecht, The Netherlands.
Vleugel
Mathijs
M
Evers
Melvin
M
Mohammed
Shabaz
S
Wulf
Phebe S
PS
Heck
Albert J R
AJ
Hoogenraad
Casper C
CC
van der Sluijs
Peter
P
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D017124:Conserved Sequence; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D018386:Kinetochores / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D051381:Rats; D012694:Serine / Q000235:genetics / Q000378:metabolism*; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism; D020692:rab3 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D050825:Synaptosomal-Associated Protein 25; D012694:Serine; C486479:Rab3c protein, mouse; D020692:rab3 GTP-Binding Proteins