title: Comparison of Cbln1 and Cbln2 functions using transgenic and knockout mice.
abstract: Cerebellin precursor protein 1 (Cbln1) is the prototype of a family of secreted neuronal glycoproteins (Cbln1-4) and its genetic elimination results in synaptic alterations in cerebellum (CB) and striatum. In CB, Cbln1 acts as a bi-functional ligand bridging pre-synaptic β-neurexins on granule cells to post-synaptic Grid2 on Purkinje neurons. Although much is known concerning the action of Cbln1, little is known of the function of its other family members. Here, we show that Cbln1 and Cbln2 have similar binding activities to β-neurexins and Grid2 and the targeted ectopic expression of Cbln2 to Purkinje cells in transgenic mice rescues the cerebellar deficits in Cbln1-null animals: suggesting that the two proteins have redundant function mediated by their common receptor binding properties. Cbln1 and Cbln2 are also co-expressed in the endolysosomal compartment of the thalamic neurons responsible for the synaptic alterations in striatum of Cbln1-null mice. Therefore, to determine whether the two family members have similar functions, we generated Cbln2-null mice. Cbln2-null mice do not show the synaptic alterations evident in striatum of Cbln1-null mice. Thus, Cbln2 can exhibit functional redundancy with Cbln1 in CB but it does not have the same properties as Cbln1 in thalamic neurons, implying one or both utilize different receptors/mechanisms in this brain region.
authors: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Yongqi
authors: Y
authors: Rong
authors: Peng
authors: P
authors: Wei
authors: Jennifer
authors: J
authors: Parris
authors: Hong
authors: H
authors: Guo
authors: Roberto
authors: R
authors: Pattarini
authors: Kristen
authors: K
authors: Correia
authors: Leyi
authors: L
authors: Li
authors: Sheila V
authors: SV
authors: Kusnoor
authors: Ariel Y
authors: AY
authors: Deutch
authors: James I
authors: JI
authors: Morgan
mesh_terms: D000818:Animals; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008247:Lysosomes / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding / Q000235:genetics; D011498:Protein Precursors / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011689:Purkinje Cells / Q000201:enzymology / Q000378:metabolism
chemical_list: C484271:CBLN1 protein, human; C558312:Cbln2 protein, mouse; D009419:Nerve Tissue Proteins; D011498:Protein Precursors