A novel phenylalanine-based targeting signal directs telencephalin to neuronal dendrites.
Neurons sort out a variety of functional molecules to appropriate subcellular destinations. Telencephalin (TLCN; intercellular adhesion molecule-5) is a cell adhesion molecule specifically localized to somatodendritic membranes in the telencephalic neurons. Here, we established a new in vivo strategy to analyze neuronal sorting mechanisms by ectopic expression of molecules of interest in the cerebellar Purkinje cells of transgenic mice. By using this system, we identified a novel dendritic targeting determinant in the cytoplasmic tail region of TLCN. A full-length TLCN ectopically expressed in the Purkinje cells was localized exclusively to dendrites but not to axons. In contrast, a deletion of cytoplasmic C-terminal 12 amino acids (residues 901-912) or a point mutation of Phe905 to Ala abrogated the dendrite-specific targeting with appearance of the truncated and point-mutated TLCN in both axons and dendrites. Furthermore, an addition of the C-terminal 17 amino acids (residues 896-912) of TLCN to an unrelated molecule (CD8) was sufficient for its specific targeting to dendrites in several types of neurons. Because the C-terminal region of TLCN does not contain any canonical dendritic targeting sequences such as the tyrosine-based motif or the dileucine motif, this study suggests a novel mechanism of protein trafficking to the dendritic compartment of neurons.
Mitsui
Sachiko
S
Laboratory for Neurobiology of Synapse, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
Saito
Michiko
M
Hayashi
Ken
K
Mori
Kensaku
K
Yoshihara
Yoshihiro
Y
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001923:Brain Chemistry; D015815:Cell Adhesion Molecules; D002462:Cell Membrane / Q000378:metabolism*; D016764:Cell Polarity; D002478:Cells, Cultured / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism*; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D010649:Phenylalanine / Q000737:chemistry*; D017354:Point Mutation; D021382:Protein Sorting Signals / Q000502:physiology*; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000502:physiology*; D011689:Purkinje Cells / Q000378:metabolism*; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000502:physiology; D016415:Sequence Alignment; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D013687:Telencephalon / Q000166:cytology
D015815:Cell Adhesion Molecules; C086747:ICAM5 protein, human; C504585:Icam5 protein, mouse; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins; D010649:Phenylalanine