Biomedical subjects

Nadder Sharif

Publications and source records attributed to Nadder Sharif.

4 recordsLinked to original sources

PubMed2006

NTS2 modulates the intracellular distribution and trafficking of NTS1 via heterodimerization.

Neurotensin (NT) receptors NTS1 and NTS2 are known to display considerable distributional overlap in mammalian central nervous system (CNS). Using co-immunoprecipitation approaches, we demonstrated here that NTS1 forms constitutive heterodimers with NTS2 in transfected COS-7 cells. We also showed that co-expression of NTS2 with NTS1 markedly decreases the cell surface density of NTS1 without affecting ERK1/2 MAPK activity or NT-induced NTS1 internalization. However, radioligand-binding studies indicated that upon prolonged NT stimulation, cell surface NTS1 receptors are more resistant to down-regulation in cells co-expressing NTS1 and NTS2 than in cells expressing NTS1 alone. Taken together, these data suggest that NTS1/NTS2 heterodimerization affects the intracellular distribution and trafficking of NTS1 by making it more similar to that of NTS2 as witnessed in cells expressing NTS2 alone. NTS1/NTS2 heterodimerization might therefore represent an additional mechanism in the regulation of NT-triggered responses mediated by NTS1 and NTS2 receptors.

Animals↗

PubMed2006

Sustained neurotensin exposure promotes cell surface recruitment of NTS2 receptors.

In this study, we investigated whether persistent agonist stimulation of NTS2 receptors gives rise to down-regulation, in light of reports that their activation induced long-lasting effects. To address this issue, we incubated COS-7 cells expressing the rat NTS2 with neurotensin (NT) for up to 24 h and measured resultant cell surface [125I]-NT binding. We found that NTS2-expressing cells retained the same surface receptor density despite efficient internalization mechanisms. This preservation was neither due to NTS2 neosynthesis nor recycling since it was not blocked by cycloheximide or monensin. However, it appeared to involve translocation of spare receptors from internal stores, as NT induced NTS2 migration from trans-Golgi network to endosome-like structures. This stimulation-induced regulation of cell surface NTS2 receptors was even more striking in rat spinal cord neurons. Taken together, these results suggest that sustained NTS2 activation promotes recruitment of intracellular receptors to the cell surface, thereby preventing functional desensitization.

Animals↗

PubMed2005

A double dissociation between sensitivity to changes in object identity and object orientation in the ventral and dorsal visual streams: a human fMRI study.

We used an event-related fMR-adaptation paradigm to investigate changes in BOLD activity in the dorsal and ventral visual streams as a function of object identity and object orientation. Participants viewed successive paired images of real-world, graspable objects, separated by a visual mask. The second image of each pair was either: (i) the same as the first image, (ii) different only in identity, (iii) different only in orientation, or (iv) different in both identity and orientation. A region in the parieto-occipital cortex (dorsal stream) showed a selective increase in BOLD activity with changes in object orientation, but was insensitive to changes in object identity. In contrast, a region in the temporo-occipital cortex (ventral stream) showed a selective increase in activity with changes in identity, but was insensitive to changes in orientation. The differential sensitivity to orientation and identity is consistent with the idea that the dorsal stream plays a critical role in the visual control of object-directed actions while the ventral stream plays a critical role in object perception.

Brain Mapping↗

PubMed2002

A temporal analysis of grasping in the Ebbinghaus illusion: planning versus online control.

Recent work has shown that pictorial illusions have a greater effect on perceptual judgements than they do on the visual control of actions, such as object-directed grasping. This dissociation between vision for perception and vision for action is thought to reflect the operation of two separate streams of visual processing in the brain. Glover and Dixon claim, however, that perceptual illusions can influence the control of grasping but that these effects are evident only at early stages of the movement. By the time the action nears its completion any effect of illusions disappears. Glover and Dixon suggest that these results are consistent with what they call a 'planning and control' model of action, in which actions are planned using a context-dependent visual representation but are monitored and corrected online using a context-independent representation. We reanalysed data from an earlier experiment on grasping in the Ebbinghaus illusion in which we showed that maximum grip aperture was unaffected by this size-contrast illusion. When we looked at these data more closely, we found no evidence for an effect of the illusion even at the earliest stages of the movement. These findings support the suggestion that the initial planning of a simple object-directed grasping movement in this illusory context is indeed refractory to the effects of the illusion. This is not to suggest that more deliberate and/or complex movements could not be influenced by contextual information.

Adult↗