Biomedical subjects

Dashi Bao

Publications and source records attributed to Dashi Bao.

5 recordsLinked to original sources

PubMed2006

Cbln1 is essential for interaction-dependent secretion of Cbln3.

Cbln1 and the orphan glutamate receptor GluRdelta2 are pre- and postsynaptic components, respectively, of a novel transneuronal signaling pathway regulating synapse structure and function. We show here that Cbln1 is secreted from cerebellar granule cells in complex with a related protein, Cbln3. However, cbln1- and cbln3-null mice have different phenotypes and cbln1 cbln3 double-null mice have deficits identical to those of cbln1 knockout mice. The basis for these discordant phenotypes is that Cbln1 and Cbln3 reciprocally regulate each other's degradation and secretion such that cbln1-null mice lack both Cbln1 and Cbln3, whereas cbln3-null mice lack Cbln3 but have an approximately sixfold increase in Cbln1. Unlike Cbln1, Cbln3 cannot form homomeric complexes and is secreted only when bound to Cbln1. Structural modeling and mutation analysis reveal that, by constituting a steric clash that is masked upon binding Cbln1 in a "hide-and-run" mechanism of endoplasmic reticulum retention, a single arginine confers the unique properties of Cbln3.

Amino Acid Sequence↗

PubMed2005

Cbln1 is essential for synaptic integrity and plasticity in the cerebellum.

Cbln1 is a cerebellum-specific protein of previously unknown function that is structurally related to the C1q and tumor necrosis factor families of proteins. We show that Cbln1 is a glycoprotein secreted from cerebellar granule cells that is essential for three processes in cerebellar Purkinje cells: the matching and maintenance of pre- and postsynaptic elements at parallel fiber-Purkinje cell synapses, the establishment of the proper pattern of climbing fiber-Purkinje cell innervation, and induction of long-term depression at parallel fiber-Purkinje cell synapses. Notably, the phenotype of cbln1-null mice mimics loss-of-function mutations in the orphan glutamate receptor, GluR delta2, a gene selectively expressed in Purkinje neurons. Therefore, Cbln1 secreted from presynaptic granule cells may be a component of a transneuronal signaling pathway that controls synaptic structure and plasticity.

Age Factors↗

PubMed2005

The structure and proteolytic processing of Cbln1 complexes.

The hexadecapeptide cerebellin is present in the brains of many vertebrate species and is derived from a larger protein, Cbln1 (cerebellin 1 precursor protein). Although cerebellin has features of a neuropeptide, Cbln1 belongs to the C1q/tumor necrosis factor superfamily of secreted proteins, suggesting that it is the biologically active molecule and the proteolytic events that generate cerebellin serve another function. Therefore, we assessed whether Cbln1 undergoes proteolytic processing and determined what consequences the cleavage events necessary to produce cerebellin have on the structure of Cbln1. Substantial degradation of Cbln1 was evident in the synaptic compartment of cerebellum and lysates of cultured cerebellar neurons and cells transfected with Cbln1 expression vectors. However, only uncleaved Cbln1 containing the cerebellin motif was released and assembled into hexameric complexes. Using yeast two hybrid and mammalian expression systems we show that the cleavages required to produce cerebellin influence the subunit stoichiometry of Cbln1 complexes. Cleavage at the N-terminus of the cerebellin sequence in Cbln1 yields trimeric complexes by separating the trimer-mediating C-terminal C1q domain from conserved N-terminal cysteine residues that mediate higher order oligomerization. Cleavage at the C-terminus of the cerebellin motif disrupts the C1q domain and abolishes subunit interactions. Functional implications of these data are discussed.

Amino Acid Sequence↗

PubMed2002

Experimental study of Eudragit mixture as a new nonadhesive liquid embolic material.

OBJECTIVE: To assess the embolic effects and biocompatibility of Eudragit mixture, a new liquid embolic agent. METHODS: In vitro, the viscosity and precipitation time of Eudragit mixtures at several concentrations were measured to study the best proportion of components of the mixture. In vivo, a branch of the right external carotid artery was embolized with Eudragit mixture in 12 rabbits, and with n-butyl cyanoacrylate in another 12 rabbits for a comparative study of the general, angiographic and histopathologic changes between the two groups. RESULTS: Eudragit mixture containing 7.5 g Eudragit, 50 ml absolute ethanol and 50 ml iopromide was shown in vitro to have good properties including rapid precipitation and soft elastic sponge formation upon contact with blood; in vivo, to be nontoxic, nonadherent to the microcatheter and able to embolize the vascular lumen completely without later recanalisation. CONCLUSION: Eudragit mixture is an effective, nontoxic, safe and promising liquid embolic agent.

Animals↗

PubMed2002

[Long-term culture and differentiation of neural stem cells of embryonic mice].

OBJECTIVES: To assess the culture and differentiation of neural stem cells in embryonic mice and set up a basis for further research in to neural stem cells. METHODS: Embryonic cortices of mice were dissociated and single cell suspensions were achieved by mechanical methods in sterile conditions, and cells were seeded in uncoated plate in N2 medium. The cells were passaged by mechanical methods, frozen and thawed by general procedure. They were identified by immunocytochemical techniques. RESULTS: Neural stem cells from embryonic mice were successfully cultured forming typical neurospheres in suspension. Neurons, astrocytes and oligodendrocytes were differentiated from neural stem cells, with a ratio of 7%, 85% - 90% and 2% - 4% respectively. CONCLUSIONS: Neural stem cells, which can be cultured and passaged steadily in vitro and they are the ideal cell sources for cell transplantation and gene therapy.

Animals↗