TY - JOUR
T1 - ZNRF Proteins Constitute a Family of Presynaptic E3 Ubiquitin Ligases
AU - Araki, Toshiyuki
AU - Milbrandt, Jeffrey
PY - 2003/10/15
Y1 - 2003/10/15
N2 - Protein ubiquitination has been implicated recently in neural development, plasticity, and degeneration. We previously identified ZNRF1/nin283, a protein with a unique, evolutionarily conserved C-terminal domain containing a juxtaposed zinc finger/RING finger combination. Here we describe the identification of a closely related protein, ZNRF2, thus defining a novel family of ZNRF E3 ubiquitin ligases. Both ZNRF1 and ZNRF2 have E3 ubiquitin ligase activity and are highly expressed in the nervous system, particularly during development. In neurons, ZNRF proteins are located in different compartments within the presynaptic terminal: ZNRF1 is associated with synaptic vesicle membranes, whereas ZNRF2 is present in presynaptic plasma membranes. Mutant ZNRF proteins with a disrupted RING finger, a domain necessary for their E3 function, can each inhibit Ca2+-dependent exocytosis in PC12 cells. These data suggest that ZNRF proteins play a role in the establishment and maintenance of neuronal transmission and plasticity via their ubiquitin ligase activity.
AB - Protein ubiquitination has been implicated recently in neural development, plasticity, and degeneration. We previously identified ZNRF1/nin283, a protein with a unique, evolutionarily conserved C-terminal domain containing a juxtaposed zinc finger/RING finger combination. Here we describe the identification of a closely related protein, ZNRF2, thus defining a novel family of ZNRF E3 ubiquitin ligases. Both ZNRF1 and ZNRF2 have E3 ubiquitin ligase activity and are highly expressed in the nervous system, particularly during development. In neurons, ZNRF proteins are located in different compartments within the presynaptic terminal: ZNRF1 is associated with synaptic vesicle membranes, whereas ZNRF2 is present in presynaptic plasma membranes. Mutant ZNRF proteins with a disrupted RING finger, a domain necessary for their E3 function, can each inhibit Ca2+-dependent exocytosis in PC12 cells. These data suggest that ZNRF proteins play a role in the establishment and maintenance of neuronal transmission and plasticity via their ubiquitin ligase activity.
KW - Endocytosis
KW - Endosome/lysosome
KW - Proteosome
KW - RING finger
KW - Spermatogenesis
KW - Synaptic transmission
UR - http://www.scopus.com/inward/record.url?scp=0142219820&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.23-28-09385.2003
DO - 10.1523/jneurosci.23-28-09385.2003
M3 - Article
C2 - 14561866
AN - SCOPUS:0142219820
SN - 0270-6474
VL - 23
SP - 9385
EP - 9394
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 28
ER -