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Although the extracellular matrix plays an important role in regulating use-dependent synaptic plasticity, the underlying molecular mechanisms are poorly understood. Here we examined the synaptic function of hyaluronic acid (HA), a major component of the extracellular matrix. Enzymatic removal of HA with hyaluronidase reduced nifedipine-sensitive whole-cell Ca 2+ currents, decreased Ca ...
In searching for binding partners of the intracellular domain of the immunoglobulin superfamily adhesion molecule CHL1, we identified the clathrin-uncoating ATPase Hsc70. CHL1 gene ablation resulted in reduced targeting of Hsc70 to the synaptic plasma membrane and synaptic vesicles, suggesting CHL1 as a synapse-targeting cue for Hsc70. CHL1 accumulates in presynaptic membranes and, in response to...
We show that the neural cell recognition molecule Close Homolog of L1 (CHL1) is required for neuronal positioning and dendritic growth of pyramidal neurons in the posterior region of the developing mouse neocortex. CHL1 was expressed in pyramidal neurons in a high-caudal to low-rostral gradient within the developing cortex. Deep layer pyramidal neurons of CHL1-minus mice were shifted to lower laminar...
In humans, defects of the corticospinal tract have been attributed to mutations in the gene encoding L1 CAM, a phenotype that is reproduced in L1-deficient mice. Using coculture assays, we report that Sema3A secreted from the ventral spinal cord repels cortical axons from wild-type but not from L1-deficient mice. L1 and neuropilin-1 (NP-1) form a stable complex, and their extracellular domains can...
To evaluate the contributions of the pre- versus postsynaptic expression of NCAM in regulation of synaptic efficacy, we cultured dissociated hippocampal cells from NCAM-deficient and wild-type mice in homo- and heterogenotypic combinations. Double recordings from synaptically coupled neurons maintained in heterogenotypic cocultures showed that synaptic strength of excitatory but not inhibitory synapses...
The myelin-associated glycoprotein (MAG) has been shown to be inhibitory for certain neurons in vitro (Mukhopadhyay et al. 1994; McKerracher et al. 1994). To investigate whether MAG is an inhibitory component in peripheral myelin in vivo, MAG-deficient mutant mice were cross-bred with C57BL/Wlds mice that have delayed lesion-induced myelin degeneration and axon regrowth. While in crushed nerves of...
The MAG-deficient mouse was used to test whether MAG acts as a significant inhibitor of axonal regeneration in the adult mammalian CNS, as suggested by cell culture experiments. Cell spreading, neurite elongation, or growth cone collapse of different cell types in vitro was not significantly different when myelin preparations or optic nerve cryosections from either MAG-deficient or wild-type mice...
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