Subunit 1 of the prefoldin chaperone complex is required for lymphocyte development and function.
Prefoldin is a hexameric chaperone that facilitates posttranslational folding of actins and other cytoskeletal proteins by the Tcp1-containing ring complex chaperonin, TriC. The present study characterized mice with a null mutation in Pfdn1, which encodes the first subunit of the Prefoldin complex. Pfdn1-deficient mice displayed phenotypes characteristic of defects in cytoskeletal function, including manifestations of ciliary dyskinesia, neuronal loss, and defects in B and T cell development and function. B and T cell maturation was markedly impaired at relatively early stages, namely at the transitions from pre-pro-B to pre-B cells in the bone marrow and from CD4-CD8- double-negative to CD4+CD8+ double-positive T cells in the thymus. In addition, mature B and T lymphocytes displayed cell activation defects upon Ag receptor cross-linking accompanied by impaired Ag receptor capping in B cells. These phenotypes illustrate the importance of cytoskeletal function in immune cell development and activation.
Department of Microbiology and Immunology, Vanderbilt University, School of Medicine, Nashville, TN 37232, USA.
Shang
S
Cao
Gianluca
G
Carlesso
Anna B
AB
Osipovich
Joan
J
Llanes
Qing
Q
Lin
Kristen L
KL
Hoek
Wasif N
WN
Khan
H Earl
HE
Ruley
D000818:Animals; D001483:Base Sequence; D001853:Bone Marrow / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology
D018832:Molecular Chaperones; D021122:Protein Subunits; C112806:prefoldin