Prefoldin 5 is required for normal sensory and neuronal development in a murine model.
Molecular chaperones and co-chaperones are crucial for cellular development and maintenance as they assist in protein folding and stabilization of unfolded or misfolded proteins. Prefoldin (PFDN), a ubiquitously expressed heterohexameric co-chaperone, is necessary for proper folding of nascent proteins, in particular, tubulin and actin. Here we show that a genetic disruption in the murine Pfdn5 gene, a subunit of prefoldin, causes a syndrome characterized by photoreceptor degeneration, central nervous system abnormalities, and male infertility. Our data indicate that a missense mutation in Pfdn5, may cause these phenotypes through a reduction in formation of microtubules and microfilaments, which are necessary for the development of cilia and cytoskeletal structures, respectively. The diversity of phenotypes demonstrated by models carrying mutations in different PFDN subunits suggests that each PFDN subunit must confer a distinct substrate specificity to the prefoldin holocomplex.
Lee
YongSuk
Y
The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Smith
Richard S
RS
Jordan
Wanda
W
King
Benjamin L
BL
Won
Jungyeon
J
Valpuesta
Jose M
JM
Naggert
Jurgen K
JK
Nishina
Patsy M
PM
D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D002490:Central Nervous System / Q000002:abnormalities / Q000378:metabolism; D005260:Female; D006801:Humans; D007006:Hypogonadism / Q000235:genetics; D008297:Male; D051379:Mice; D008870:Microtubules / Q000235:genetics / Q000378:metabolism; D023421:Models, Animal; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016296:Mutagenesis; D020125:Mutation, Missense / Q000187:drug effects; D009607:Nitrosourea Compounds / Q000494:pharmacology; D017354:Point Mutation / Q000187:drug effects; D011487:Protein Conformation; D055211:Retinal Photoreceptor Cell Inner Segment / Q000378:metabolism; D055214:Retinal Photoreceptor Cell Outer Segment / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism*
D018832:Molecular Chaperones; D009607:Nitrosourea Compounds; C112806:prefoldin