Characterisation of amphioxus protein kinase C-δ/θ reveals a unique proto-V3 domain suggesting an evolutionary mechanism for PKC-θ unique V3. Issue 84 (January 2019)

• Record Type: Journal Article
• Authors: Chen, Zhi-long; Gong, Bei-Ni; Wang, Qi-long; Xiao, Zhi-hui; Deng, Chong; Wang, Wen-qian; Li, Yingqiu
• Is Part Of: Fish & shellfish immunology. Issue 84(2019)
• Page Start: 1100
• Page End: 1107
• Publication Date: 2019-01
• Subjects: Amphioxus -- BbPKC-δ/θ -- PKC-θ V3 domain -- Proto-V3 domain -- PxxP motif -- Immunological synapse -- NF-κB activation -- T-cell activation -- Evolutionary mechanism; Fishes -- Immunology -- Periodicals; Shellfish -- Immunology -- Periodicals; Poissons -- Immunologie -- Périodiques; Crustacés -- Immunologie -- Périodiques; 571.9617
• DOI: 10.1016/j.fsi.2018.11.001
• Languages: English
• ISSNs: 1050-4648

Abstract

Abstract: A primitive adaptive immune system has recently been suggested to be present in a basal chordate amphioxus ( Branchiostoma belcheri, Bb), making it an ideal model for studying the origin of adaptive immune. The novel protein kinase C isoform PKC-θ, but not its closest isoform PKC-δ, plays a critical role for mammalian T-cell activation via translocation to immunological synapse (IS) mediated by a unique PKC-θ V3 domain containing one PxxP motif. To understand the evolution of this unique PKC-θ V3 domain and the primitive adaptive immune system in amphioxus, we comparatively studied the orthologs of PKC-δ and -θ from amphioxus and other species. Phylogenetic analysis showed BbPKC-δ/θ to be the common ancestor of vertebrate PKC-δ and PKC-θ, with a V3 domain containing two PxxP motifs. One motif is conserved in both zebrafish and mammalian PKC-θ but is absent in PKC-δ V3 domain of these species, and has already emerged in drosophila PKC-δ. The other non-conserved motif emerged in BbPKC-δ/θ, and only retained in Danio rerio PKC-δ (DrPKC-δ) but lost in mammalian PKC-δ and -θ. Comparative analyses of the sequence and function of BbPKC-δ/θ, DrPKC-δ, DrPKC-θ and Homo sapiens PKC-θ (HsPKC-θ) in IS translocation and T-cell receptor (TCR)-induced NF-κB activation revealed that retention of the conserved PxxP motif and loss of the non-conserved PxxP motif in mammalian PKC-θ and loss of both PxxP motifs in mammalian PKC-δ accomplish the unique function of PKC-θ in T cells. Together, this study suggests an evolutionary mechanism for PKC-θ unique V3 and reveals BbPKC-δ/θ is the common ancestor of PKC-δ and -θ with a functional proto-V3 domain, supplying new evidence for the existence of primitive adaptive immune system in amphioxus. Highlights: Cloning and sequence analysis of Branchiostoma belcheri PKC-δ/θ (BbPKC-δ/θ). BbPKC-δ/θ is the common ancestor of vertebrate PKC-δ and PKC-θ. BbPKC-δ/θ translocates to immune synapse and promotes NF-κB activity in T cells. BbPKC-δ/θ has a functional proto-V3 domain with two essential PxxP motifs. Evolutionary retention or loss of PxxP motifs may lead to PKC-θ unique V3 domain.