Transient aggregation of major histocompatibility complex class II chains during assembly in normal spleen cells.
Many cell surface proteins exist as complexes of multiple subunits. It is well established that most such complexes are assembled within the endoplasmic reticulum (ER). However, the mechanistic details of the assembly process are largely unknown. We show here that alpha and beta subunits of major histocompatibility complex class II antigens in spleen cells of normal mice pass through a transiently aggregated phase in the ER prior to assembly with the invariant chain (Ii). Aggregates form immediately after synthesis and disappear concomitantly with assembly of mature alpha beta Ii complexes. In spleen cells lacking Ii, aggregates fail to be efficiently dissociated over time, implicating subunit assembly as a requirement for disaggregation. Two ER chaperones, BiP and calnexin, bind to newly synthesized class II MHC chains but do not contribute appreciably to the large size of the aggregates. Our observations suggest that some subunits of multisubunit complexes pass through a transient, dynamic high molecular weight aggregate phase during the physiological process of assembly. The results further suggest a novel role for Ii in promoting stable dissociation of preformed aggregates containing alpha and beta subunits rather than in preventing their formation.
Marks
M S
MS
Cell Biology and Metabolism Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA.
Germain
R N
RN
Bonifacino
J S
JS
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte; D002135:Calcium-Binding Proteins / Q000378:metabolism; D037281:Calnexin; D002352:Carrier Proteins / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000378:metabolism*; D046911:Macromolecular Substances; D051379:Mice; D008810:Mice, Inbred C57BL; D018832:Molecular Chaperones / Q000378:metabolism; D008970:Molecular Weight; D013154:Spleen / Q000378:metabolism*; D013997:Time Factors
D000944:Antigens, Differentiation, B-Lymphocyte; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D000949:Histocompatibility Antigens Class II; D046911:Macromolecular Substances; D018832:Molecular Chaperones; C045084:invariant chain; D037281:Calnexin; D000255:Adenosine Triphosphate