Axonal transport of two major components of the ubiquitin system: free ubiquitin and ubiquitin carboxyl-terminal hydrolase PGP 9.5

Bizzi, Alberto; Schaetzle, B.; Patton, A.; Gambetti, Pierluigi; Autilio-Gambetti, L.

doi:10.1016/0006-8993(91)91135-n

Cited by 44 publications

(23 citation statements)

References 48 publications

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“…Cytosolic localization of ubiquitin has also been reported in other cell types [36]. The association of free ubiquitin and PGP 9.5 with the slow component b, which transports cytoplasmic enzymes but not membranous structures through the axon [37], also is consistent with the cytosolic location of these proteins.…”

Section: Discussionmentioning

confidence: 50%

Light and Electron Microscopic Immunohistochemical Localization of Protein Gene Product 9.5 and Ubiquitin Immunoreactivities in the Human Epididymis and Vas Deferens1

Fraile

Martı́n²,

Miguel

et al. 1996

Biology of Reproduction

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The distribution of protein gene product 9.5 (PGP) and ubiquitin immunoreactivities in the ductuli efferentes, ductus epididymidis, and ductus deferens of humans was studied by Western blot analyses and light and electron microscopic immunocytochemistry. PGP immunoreactivity was intense in the ductuli efferentes and weak in the ductus epididymidis and ductus deferens, while ubiquitin immunoreactivity was intense in the ductuli efferentes and ductus epididymidis and very weak in the ductus deferens. In the ductuli efferentes epithelium, PGP immunolabeling was observed in the cytoplasm of principal cells, whereas ubiquitin immunoreactivity was found in the nucleus and cytoplasm of principal cells and ciliated cells. In the ductus epididymidis epithelium, only scattered cells (mitochondria-rich cells) showed PGP immunoreaction in their cytoplasm, whereas ubiquitin immunostaining was detected in the nucleus and cytoplasm of most epithelial cells, except for the cauda, where ubiquitin immunolabeling was observed only in the nuclei. The ductus deferens showed no immunostaining for PGP, and only nuclear immunoreactivity to ubiquitin. The ultrastructural localization of PGP immunoreactivity was in the apical cytosol and microvilli. In addition to these locations, ubiquitin immunoreactivity was also found in the nucleus of all cell types and cilia of ciliated cells. Although the distribution of PGP and ubiquitin immunoreactivities in humans differs from that reported in rats, it seems that PGP and ubiquitinated proteins are secreted into the epididymal lumen in both species.

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Section: Discussionmentioning

confidence: 50%

Light and Electron Microscopic Immunohistochemical Localization of Protein Gene Product 9.5 and Ubiquitin Immunoreactivities in the Human Epididymis and Vas Deferens1

Fraile

Martı́n²,

Miguel

et al. 1996

Biology of Reproduction

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“…Protein gene product 9.5 is an abundant, predominantly neuronal form of ubiquitin C-terminal hydrolase, a. cytosolic enzyme that removes ubiquitin (Wilkinson et al, 1989). It is transported within the slow component (SCB) of axonal transport (Bizzi et al, 1991). In spite of the abundance of this form of ubiquitin hydrolase in normal cutaneous nerves, we did not identify immunostaining for ubiquitin in axons, and the neurobiological significance of the large amount of PGP within the axons remains unknown.…”

Section: H S I E H C H O I L I N C H a N G M C A R T H U R A mentioning

confidence: 89%

Epidermal denervation and its effects on keratinocytes and Langerhans cells

et al. 1996

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SummarySkin innervation has been considered to subserve sensory perception only, but several lines of evidence suggest that there are 'effector' influences of skin innervation on the immune system and keratotinocytes. In this study, we transected the sciatic nerves of rats and examined the effects of denervation on the epidermis. In normal skin, the epidermis was densely innervated by fine axons that were immunostained with several axonal markers, including neuronal ubiquitin carboxyl terminal hydrolase (protein gene product 9.5). All of the epidermal axons in the regions innervated by sciatic nerve disappeared within 24-48 h after transection of sciatic nerve, and remained absent as long as subsequent reinnervation by regenerating axonal sprouts was prevented. Denervation produced changes in both the keratinocytes and the Langerhans cells, the bone marrowderived antigen-presenting cells of the epidermis. The thickness of epidermis decreased within 7 days. By 48h after transection, the Langerhans cells and their dendritic processes became intensely immunoreactive for protein gene product. Protein gene product 9.5 expression on Langerhans cells remained prominent as long as skin was denervated, but disappeared with reinnervation. By reverse transcription-polymerase chain reaction, we demonstrated the presence of the transcripts for protein gene product 9.5 in epidermis, consistent with the synthesis of the protein by the Langerhans cells. We conclude that epidermal sensory fibres have novel influences on both keratinocytes and Langerhans cells of the epidermis.

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“…Preliminary evidence suggests, however, that ROS contain characteristic Ub C-terminal isopeptidase/hydrolase activities distinct from those in other retinal cells. We propose that ROS are distinguished by (i) relatively high levels of Ubal-insensitive isopeptidase(s) (see above); (ii) the demonstrated absence of Ub C-terminal hydrolase PGP 9.5, present in high concentrations elsewhere in the retina (67,68); and because ROS are not sites of protein synthesis, (iii) the absence of Ub C-terminal ␣-NH 2 -protein hydrolase activity required for the processing of Ub gene products (29). The particular Ub C-terminal isopeptidase/hydrolase activities in ROS presumably reflect the highly specialized function of photoreceptor cell outer segments.…”

Section: Characterization Of Ros Ub C-terminal Isopeptidase/hydrolasementioning

confidence: 97%

Ubiquitinylation and Ubiquitin-dependent Proteolysis in Vertebrate Photoreceptors (Rod Outer Segments)

Obin

Jahngen-Hodge

Nowell

et al. 1996

Journal of Biological Chemistry

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In corroboration of the hypothesized regulation of phototransduction proteins by the ubiquitin-dependent pathway, we identified free ubiquitin (8 kDa) and ubiquitin-protein conjugates (50 to >200 kDa; pI 5.3-6.8 by two-dimensional electrophoresis) in bovine rod outer segments (ROS). A 38-kDa ubiquitinylated protein and transducin (Gt) were eluted together from light-adapted ROS membranes with GTP. When ROS were dark-adapted, this 38-kDa ubiquitinylated species and Gt were readily solubilized in buffer lacking GTP. These data are consistent with ubiquitinylation of Gt and corroborate previous cell-free experiments identifying Gt as a substrate for ubiquitin-dependent proteolysis (Obin, M. S., Nowell, T., and Taylor, A. (1994) Biochem. Biophys. Res. Commun. 200, 1169-1176). Evidence for ubiquitinylation of rhodopsin (36 kDa), the (photo)receptor coupled to Gt, included (i) the presence in ROS membranes "stripped" of peripheral membrane proteins of numerous ubiquitin-protein conjugates, including two whose masses (44 and 50 kDa) are consistent with mono- and diubiquitinylated rhodopsin; (ii) catalysis by permeabilized ROS of 125I-labeled ubiquitin-protein conjugates whose masses (42, 50, and 58 kDa) suggest a "ladder" of mono-, di-, and triubiquitinylated rhodopsin; (iii) parallel mobility shifts on SDS-polyacrylamide gels of rhodopsin and these 125I-labeled ubiquitin-protein conjugates; and (iv) generation of enhanced levels of 125I-labeled ubiquitin-protein conjugates when stripped, detergent-solubilized ROS membranes (95% rhodopsin) were incubated with reticulocyte lysate. A functional ubiquitin-dependent pathway in ROS is demonstrated by the presence of (i) the ubiquitin-activating enzyme (E1); (ii) four ubiquitin carrier proteins (E214K, E220K, E225K, and E235K) and pronounced activity of E214K, an enzyme required for "N-end rule" proteolysis; (iii) ATP-dependent 26 S proteasome activity that rapidly degrades high mass 125I-labeled ubiquitin-ROS protein conjugates; and (iv) distinct ubiquitin C-terminal isopeptidase/hydrolase activities, including potent ubiquitin-aldehyde-insensitive activity directed at high mass ubiquitinylated moieties. Considered together, the data support a novel role for the ubiquitin-dependent pathway in the regulation of mammalian phototransduction protein levels and/or activities and provide the first identification of a non-calpain proteolytic system in photoreceptors.

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Axonal transport of two major components of the ubiquitin system: free ubiquitin and ubiquitin carboxyl-terminal hydrolase PGP 9.5

Cited by 44 publications

References 48 publications

Light and Electron Microscopic Immunohistochemical Localization of Protein Gene Product 9.5 and Ubiquitin Immunoreactivities in the Human Epididymis and Vas Deferens1

Light and Electron Microscopic Immunohistochemical Localization of Protein Gene Product 9.5 and Ubiquitin Immunoreactivities in the Human Epididymis and Vas Deferens1

Epidermal denervation and its effects on keratinocytes and Langerhans cells

Ubiquitinylation and Ubiquitin-dependent Proteolysis in Vertebrate Photoreceptors (Rod Outer Segments)

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