Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously demonstrated that the in vivo vitreal injection of an antisense oligonucleotide directed to the kinesin heavy chain inhibits retinal kinesin synthesis by 82% and concomitantly inhibits rapid transport of total protein into the optic nerve by 70%. These results establish a major role for kinesin in rapid axonal transport in vivo. Recently, the cloning of a family of kinesin-like molecules from the mammalian brain has been reported, and some of these proteins are also expressed in neurons. To assign to specific function to the kinesin heavy chain we inhibited the kinesin synthesis with an antisense kinesin oligonucleotide and assessed the axonal transport into the optic nerve of representative proteins from each of three vesicle classes that contain rapidly transported proteins. Marker proteins used were substance P for peptide-containing synaptic vesicles, the amyloid protein for plasma membrane precursor vesicles, and several integral synaptic vesicle proteins. Our results indicate that the major anterograde motor protein for all three vesicle classes utilizes kinesin heavy chain, although we discuss alternative explanations.
 ...
PMID:Inhibition of kinesin synthesis in vivo inhibits the rapid transport of representative proteins for three transport vesicle classes into the axon. 753 13

The functional significance of biochemical and immunochemical heterogeneity in neuronal kinesin remains uncertain. Confocal laser scanning microscopy, cytofluorimetric scanning, and immunoblots were used for quantitative analyses of axonal transport and cellular distribution of immunochemically distinct kinesin heavy chain isoforms (H1 and H2) in rat peripheral nerve and spinal cord. H1 and H2 immunoreactivities (IR) were observed in axons proximal to a crush as early as 1 hr after the crush operation and increased linearly with time, consistent with fast axonal transport of both. Only approximately 10% of the proximal accumulations of H1-IR and H2-IR accumulated distal to the crush, in contrast to synaptophysin-IR (approximately 70%). H2-IR was widely present in peripheral nervous system and virtually colocalized with synaptic vesicle proteins synaptophysin, synaptobrevin I, and SNAP-25 and two neuropeptides [calcitonin gene-related peptide (CGRP) and substance P (SP)], although H2-IR was weaker in spinal cord terminals. In contrast, H1-IR appeared preferentially enriched in large axons, probably motor and large sensory neurons, which contained synaptophysin-IR, synaptobrevin I-IR, SNAP-25-IR, and CGRP-IR. However, H1-IR was weak or absent from SP-containing thin and medium-sized axons. In addition, H1-IR appeared to be absent from spinal cord nerve terminals. H1- and H2-IR kinesins are both transported with fast axonal transport, and comparatively small amounts of kinesins are retrogradely transported. H2 was widely distributed in motor, sensory, and sympathetic neurons, whereas H1 was enriched in large motor and sensory neurons.
 ...
PMID:Axonal transport and distribution of immunologically distinct kinesin heavy chains in rat neurons. 1050 79

In neurons, neuropeptides and other synaptic components are transported down the axon to the synapse in vesicles using molecular motors of the kinesin family. In the synapse, these neuropeptides are found in dense core vesicles (DCVs), and, following calcium-mediated exocytosis, they interact with receptors on the target cell. We have developed a rapid, large-scale technique for purifying peptide-containing DCVs from specific nuclei in the central nervous system. By using differential velocity gradient and equilibrium gradient centrifugation, neuropeptide-containing DCVs can be separated by size and density from optic nerve (ON) and its termini, the lateral geniculate nuclei and the superior colliculi. Isolated DCVs contain neuropeptides (substance P and brain-derived neurotrophic factor), synaptic vesicle (SV) membrane proteins (SV2, synaptotagmins, synaptophysin, Rab3 and synaptobrevin), SV-associated proteins (alpha-synuclein), secretory markers for DCVs previously isolated (secretogranin II), and beta-amyloid precursor protein. By using electron microscopic techniques, DCV were also visualized and shown to be immunoreactive for neuropeptides, neurotrophins, and SV membrane proteins. Because of the interesting group of physiological and potentially pathophysiological proteins associated with these vesicles; this isolation procedure, applicable to other CNS nuclei, should represent an important research tool.
 ...
PMID:Isolation and characterization of substance P-containing dense core vesicles from rabbit optic nerve and termini. 1110 68