TY - JOUR
T1 - Analysis of Gga null mice demonstrates a non-redundant role for mammalian GGA2 during development
AU - Govero, Jennifer
AU - Doray, Balraj
AU - Bai, Hongdong
AU - Kornfeld, Stuart
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2012/1/26
Y1 - 2012/1/26
N2 - Numerous studies using cultured mammalian cells have shown that the three GGAs (Golgi-localized, gamma-ear containing, ADP-ribosylation factor- binding proteins) function in the transport of cargo proteins between the trans- Golgi network and endosomes. However, the in vivo role(s) of these adaptor proteins and their possible functional redundancy has not been analyzed. In this study, the genes encoding GGAs1-3 were disrupted in mice by insertional mutagenesis. Loss of GGA1 or GGA3 alone was well tolerated whereas the absence of GGA2 resulted in embryonic or neonatal lethality, depending on the genetic background of the mice. Thus, GGA2 mediates a vital function that cannot be compensated for by GGA1and/or GGA3. The combined loss of GGA1 and GGA3 also resulted in a high incidence of neonatal mortality but in this case the expression level of GGA2 may be inadequate to compensate for the loss of the other two GGAs. We conclude that the three mammalian GGAs are essential proteins that are not fully redundant.
AB - Numerous studies using cultured mammalian cells have shown that the three GGAs (Golgi-localized, gamma-ear containing, ADP-ribosylation factor- binding proteins) function in the transport of cargo proteins between the trans- Golgi network and endosomes. However, the in vivo role(s) of these adaptor proteins and their possible functional redundancy has not been analyzed. In this study, the genes encoding GGAs1-3 were disrupted in mice by insertional mutagenesis. Loss of GGA1 or GGA3 alone was well tolerated whereas the absence of GGA2 resulted in embryonic or neonatal lethality, depending on the genetic background of the mice. Thus, GGA2 mediates a vital function that cannot be compensated for by GGA1and/or GGA3. The combined loss of GGA1 and GGA3 also resulted in a high incidence of neonatal mortality but in this case the expression level of GGA2 may be inadequate to compensate for the loss of the other two GGAs. We conclude that the three mammalian GGAs are essential proteins that are not fully redundant.
UR - http://www.scopus.com/inward/record.url?scp=84856246280&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0030184
DO - 10.1371/journal.pone.0030184
M3 - Article
C2 - 22291915
AN - SCOPUS:84856246280
VL - 7
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 1
M1 - e30184
ER -