The p24 family member p23 is required for early embryonic development.
The p24 family of type I integral-membrane proteins, which are localised in the endoplasmic reticulum (ER), the intermediate compartment and the Golgi apparatus, are thought to function as receptors for cargo exit from the ER and in transport vesicle formation. Members of the p24 family have been found in a molecular complex and are enriched in COPI-coated vesicles, which are involved in membrane traffic between the ER and Golgi complex. Although expressed abundantly, simultaneous deletion of several family members does not appear to affect cell viability and protein secretion in yeast. In order to gain more insights into the physiological roles of different p24 proteins, we generated mice deficient in the expression of one family member, p23 (also called 24delta1, see for alternative nomenclature). In contrast to yeast genetics, in mice disruption of both p23 alleles resulted in early embryonic lethality. Inactivation of one allele led not only to reduced levels of p23 itself but also to reduced levels of other family members. The reduction in steady-state protein levels also induced structural changes in the Golgi apparatus, such as the formation of dilated saccules. The generation of mice deficient in p23 expression has revealed an essential and non-redundant role for p23 in the earliest stages of mammalian development. It has also provided genetic evidence for the participation of p24 family members in oligomeric complexes and indicates a structural role for these proteins in maintaining the integrity of the early secretory pathway.
Denzel
A
A
Imperial Cancer Research Fund, London, UK.
Otto
F
F
Girod
A
A
Pepperkok
R
R
Watson
R
R
Rosewell
I
I
Bergeron
J J
JJ
Solari
R C
RC
Owen
M J
MJ
D000483:Alleles; D000818:Animals; D001692:Biological Transport; D015152:Blotting, Northern; D015153:Blotting, Western; D018699:Coated Vesicles / Q000378:metabolism*; D020756:Coatomer Protein / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D018390:Gene Targeting; D005804:Genes, Lethal; D005838:Genotype; D006056:Golgi Apparatus / Q000378:metabolism* / Q000648:ultrastructure; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D005810:Multigene Family; D018160:Receptors, Cytoplasmic and Nuclear; D013347:Subcellular Fractions / Q000737:chemistry
C108779:BHKp23 protein, mammalian; D020756:Coatomer Protein; D046911:Macromolecular Substances; D008565:Membrane Proteins; D018160:Receptors, Cytoplasmic and Nuclear