scholarly journals Cbln1 Is Essential for Interaction-Dependent Secretion of Cbln3

2006 ◽  
Vol 26 (24) ◽  
pp. 9327-9337 ◽  
Author(s):  
Dashi Bao ◽  
Zhen Pang ◽  
Marc A. Morgan ◽  
Jennifer Parris ◽  
Yongqi Rong ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Glutamate Receptor ◽  
Knockout Mice ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Structure And Function ◽  
Related Protein ◽  
Cerebellar Granule ◽  
Steric Clash ◽  
And Function

ABSTRACT Cbln1 and the orphan glutamate receptor GluRδ2 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.

scholarly journals Recent advances in understanding the mechanisms of cerebellar granule cell development and function and their contribution to behavior

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1142 ◽  
Author(s):  
Elizabeth P. Lackey ◽  
Detlef H. Heck ◽  
Roy V. Sillitoe
Keyword(s):  
Granule Cell ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Expression Patterns ◽  
Cell Lineage ◽  
Autism Spectrum ◽  
Cerebellar Granule ◽  
Motor Behaviors ◽  
Recent Advances ◽  
And Function

The cerebellum is the focus of an emergent series of debates because its circuitry is now thought to encode an unexpected level of functional diversity. The flexibility that is built into the cerebellar circuit allows it to participate not only in motor behaviors involving coordination, learning, and balance but also in non-motor behaviors such as cognition, emotion, and spatial navigation. In accordance with the cerebellum’s diverse functional roles, when these circuits are altered because of disease or injury, the behavioral outcomes range from neurological conditions such as ataxia, dystonia, and tremor to neuropsychiatric conditions, including autism spectrum disorders, schizophrenia, and attention-deficit/hyperactivity disorder. Two major questions arise: what types of cells mediate these normal and abnormal processes, and how might they accomplish these seemingly disparate functions? The tiny but numerous cerebellar granule cells may hold answers to these questions. Here, we discuss recent advances in understanding how the granule cell lineage arises in the embryo and how a stem cell niche that replenishes granule cells influences wiring when the postnatal cerebellum is injured. We discuss how precisely coordinated developmental programs, gene expression patterns, and epigenetic mechanisms determine the formation of synapses that integrate multi-modal inputs onto single granule cells. These data lead us to consider how granule cell synaptic heterogeneity promotes sensorimotor and non-sensorimotor signals in behaving animals. We discuss evidence that granule cells use ultrafast neurotransmission that can operate at kilohertz frequencies. Together, these data inspire an emerging view for how granule cells contribute to the shaping of complex animal behaviors.

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