Biomedical subjects

William D Phillips

Publications and source records attributed to William D Phillips.

5 recordsLinked to original sources

PubMed2006

Neural agrin: a synaptic stabiliser.

Neural agrin is a heparan sulphate proteoglycan first defined by its ability to induce the clustering of acetylcholine receptors (AChRs) on cultured muscle cells. Neural agrin activates the transmembrane Muscle Specific Kinase (MuSK) on the postsynaptic muscle cell to stabilise the developing neuromuscular synapse. Three biological mechanisms for agrin/MuSK signalling are briefly discussed: selective transcription of synaptic genes such as MuSK itself, to reinforce developing postsynaptic clusters of AChRs; initiation of second messenger signalling pathways that can induce the formation of AChR clusters and retrograde signalling downstream of agrin/MuSK that may transform the growth cone of the motor axon into a stable differentiated nerve terminal, specialised for regulated exocytosis of neurotransmitter. Here we briefly review some key mechanisms through which neural agrin acts to foster the formation of mature neuromuscular synapses.

Agrin↗

PubMed2005

Bose-Einstein condensates and precision measurements.

An ongoing challenge in physics is to make increasingly accurate measurements of physical quantities. Bose-Einstein condensates in atomic gases are ideal candidates for use in precision measurement schemes since they are extremely cold and have laser-like coherence properties. In this paper, we review these two attributes and discuss how they could be exploited to improve the resolution in a range of different measurements.

Computer Simulation↗

PubMed2004

Increased ratio of rapsyn to ACh receptor stabilizes postsynaptic receptors at the mouse neuromuscular synapse.

The metabolic turnover of nicotinic ACh receptors (AChR) at the neuromuscular synapse is regulated over a tenfold range by innervation status, muscle electrical activity and neural agrin, but the downstream effector of such changes has not been defined. The AChR-associated protein rapsyn is essential for forming AChR clusters during development. Here, rapsyn was tagged with enhanced green fluorescent protein (EGFP) to begin to probe its influence at the adult synapse. In C2 myotubes, rapsyn-EGFP participated with AChR in agrin-induced AChR cluster formation. When electroporated into the tibialis anterior muscle of young adult mice, rapsyn-EGFP accumulated in discrete subcellular structures, many of which colocalized with Golgi markers, consistent with the idea that rapsyn assembles with AChR in the exocytic pathway. Rapsyn-EGFP also targeted directly to the postsynaptic membrane where it occupied previously vacant rapsyn binding sites, thereby increasing the rapsyn to AChR ratio. At endplates displaying rapsyn-EGFP, the metabolic turnover of AChR (labelled with rhodamine-alpha-bungarotoxin) was slowed. Thus, the metabolic half-life of receptors at the synapse may be modulated by local changes in the subsynaptic ratio of rapsyn to AChR.

Animals↗

PubMed2004

Neuregulin potentiates agrin-induced acetylcholine receptor clustering in myotubes.

Agrin and neuregulin (HRG-beta1) play complementary roles in synapse formation. While HRG-beta1 induces transcriptional up-regulation of postsynaptic proteins, here we present evidence that it can potentiate agrin-induced acetylcholine receptor (AChR) clustering in C2 myotubes. Agrin induced maximal AChR clustering in 4 h. HRG-beta1 treatment for 4 h produced no increase over basal AChR cluster numbers. When myotubes were treated for 4 h with 100 pM agrin, HRG-beta1 augmented AChR cluster numbers by 2-fold compared to myotubes treated with 100 pM agrin alone. Thus, HRG-beta1 can potentiate agrin-induced AChR clustering.

Agrin↗

PubMed2002

GABARAP and GABA(A) receptor clustering.

Coyle et al. (2002), in this issue of Neuron, reveal the crystal structure for the GABA(A) receptor binding protein, GABARAP. They show GABARAP can switch from a monomer to an extended linear polymer form that may function to assemble microtubules during the intracellular trafficking or postsynaptic clustering of GABA(A) receptors.

Adaptor Proteins, Signal Transducing↗