title: Agrin is involved in lymphocytes activation that is mediated by alpha-dystroglycan.
abstract: It is well established that agrin, an extracellular matrix protein, plays a crucial role in the formation of neuromuscular junctions. Recent evidence indicates that agrin also contributes to immunological synapse formation. However, little is known about how agrin induces the activation of lymphocytes and whose receptors mediate its regulatory effects on these cells. In the present study, agrin was detected in lymphocytes. Up-regulation of agrin expression was involved in lymphocyte activation whereas down-regulation of its expression led to inhibition of both antigen-specific and nonspecific lymphocyte activation, indicating an intrinsic role for agrin in the activation of lymphocytes. Unexpectedly, unlike that found in muscle cells where there is coexpression of muscle-specific kinase (MuSK) and alpha-dystroglycan receptors for agrin, only alpha-dystroglycan could be detected in lymphocytes. Confocal examination showed that alpha-dystroglycan colocalized with agrin in forming the immunological synapse. Down-regulation of alpha-dystroglycan expression inhibited lymphocyte activation even in the presence of agrin. However, agrin involved in down-regulation of alpha-dystroglycan receptors did not increase the inhibitory effect on lymphocytes activation. The anti-alpha-dystroglycan antibody also induced lymphocytes activation. Taken together, these findings strongly indicate that agrin and alpha-dystroglycan mediate lymphocyte activation. Furthermore, agrin-involved lymphocyte activation is mediated by alpha-dystroglycan.
authors.affiliation: Department of Immunology, Shanghai Medical College of Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Chu
authors.forename: Liping
authors.initials: L
authors.lastname: Su
authors.forename: Yanping
authors.initials: Y
authors.lastname: Gong
authors.forename: Ruihua
authors.initials: R
authors.lastname: Zhang
authors.forename: Sidong
authors.initials: S
authors.lastname: Xiong
mesh_terms: D018171:Agrin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D049030:Dystroglycans / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D007365:Intercellular Junctions / Q000378:metabolism; D008213:Lymphocyte Activation / Q000502:physiology*; D008214:Lymphocytes / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D021381:Protein Transport; D017978:Receptors, Growth Factor / Q000378:metabolism
chemical_list: D018171:Agrin; D017978:Receptors, Growth Factor; C080030:agrin receptor; D049030:Dystroglycans