Tips from The Journal of Neuroscience

June 27, 2006

1. Will the Real Tip-Link Antigen Please Stand Up
Zubair M. Ahmed, Richard Goodyear, Saima Riazuddin, Ayala Lagziel, P. Kevin Legan, Martine Behra, Shawn M. Burgess, Kathryn S. Lilley, Edward R. Wilcox, Sheikh Riazuddin, Andrew J. Griffith, Gregory I. Frolenkov, Inna A. Belyantseva, Guy P. Richardson, and Thomas B. Friedman

The tip link sits at the business end of a hair cell, linking the top of a shorter stereocilia on the hair bundle to its taller neighbor, and thus presumably gating the mechanosensitive channels. This week, Ahmed et al. set out to identify the protein previously known as the tip-link antigen (TLA). Using mass spectrometric analysis of TLA, the authors identified TLA as protocadherin-15. The isoforms of protocadherin-15 had distinct C-terminal domains (CD1, CD2, and CD3). The distribution of two of the isoforms suggested that they are part of the tip-link complex, probably serving as anchoring elements rather than the central strand. Protocadherin-15-CD3 immunoreactivity was found at the basal end where the tip link attaches to the shorter stereocilia, and CD1 immunoreactivity was found at the distal end where the tip link attaches to the taller sterocilium. Calcium chelation, known to remove tip links and abolish mechanotransduction, also caused loss of CD3 immunoreactivity.

2. Interneuronal Migration Sans Reelin
Ramón Pla, Víctor Borrell, Nuria Flames, and Oscar Marín

This week, Pla et al. argue that interneurons, unlike cortical projection neurons, migrate to their cortex locations without Reelin, the secreted product of Cajal-Retzius cells. Cortical interneurons originate in the median ganglionic eminence(MGE), migrate tangentially to cortex, and then radially to their final laminar position. The authors report that mice lacking Dab1, the intracellular adaptor protein necessary for Reelin signaling, had impaired laminar distribution, but the tangential migration was normal. To study the laminar migration, the authors used microtransplantation to graft embryonic day 12.5 (E12.5) or E15 interneurons into the MGE of E12 or E15 hosts. The resulting lamination depended on the age of the grafted interneurons and to a lesser extent the age of the host, seemingly incompatible with direct Reelin signaling. Grafts of Dab1-/- neurons into wild-type hosts also displayed normal lamination. Because interneurons reach their final position after projection neurons, the authors suggest that they are guided by cues from the projection neurons rather than Reelin.

3. Bimanual Motor Learning
Paul M. Bays and Daniel M. Wolpert

Bays and Wolpert examined our ability to predict and oppose external forces in order to maintain limb or body position. They chose a bimanual task in which a force was applied to the left hand based on the velocity of the right hand. Subjects learned to predict and oppose the force to keep the left hand steady. This task dissociates the representation of the motion that determined the force from the representation of the force itself. After practice reduced the errors in left-hand position, the authors made life complicated by altering the joint configuration of the right or left arm. Interesting, the learned transformation from movement to force involved different coordinate systems for the two hands. The right hand movement was represented as "extrinsic" coordinates, related to the hand velocity, whereas the force generated in the left hand was represented as "intrinsic" coordinates related to expected joint torques.

4. CHIP-Less Mice Accumulate Tau
Chad A. Dickey, Mei Yue, Wen-Lang Lin, Dennis W. Dickson, Judith H. Dunmore, Wing C. Lee, Cynthia Zehr, Gemma West, Songsong Cao, Amber M. K. Clark, Guy A. Caldwell, Kim A. Caldwell, Christopher Eckman, Cam Patterson, Michael Hutton, and Leonard Petrucelli

The accumulation of the microtubule-associated protein tau is associated with several neurodegenerative diseases, and in the case of FTDP-17 (frontotemporal dementia with parkinsonism-linked to chromosome 17), tau mutations are sufficient to produce neurodegeneration. This week, Dickey et al. focused on the role of the cochaperone and ubiquitin ligase CHIP (C terminus of the Hsc70-interacting protein) in degradation of phosphorylated tau. In CHIP-/- mice, about half of the knock-out mice showed motor deficits and small size. These symptomatic knock-out mice had elevated tau levels and thus were used for the experiments. In these mice, there was an accumulation of non-aggregated, ubiquitin-negative, hyperphosphorylated tau. Overexpression of mutant human tau (P301L) caused accumulation of phospho-tau but was not sufficient to produce aggregates or "pre-tangle" structures. Thus, the authors suggest that polyubiquitination of tau by CHIP contributes to insoluble tau aggregates and is part of an adaptive neuronal response.

Society for Neuroscience

Related Neurons Articles from Brightsurf:

Paying attention to the neurons behind our alertness
The neurons of layer 6 - the deepest layer of the cortex - were examined by researchers from the Okinawa Institute of Science and Technology Graduate University to uncover how they react to sensory stimulation in different behavioral states.

Trying to listen to the signal from neurons
Toyohashi University of Technology has developed a coaxial cable-inspired needle-electrode.

A mechanical way to stimulate neurons
Magnetic nanodiscs can be activated by an external magnetic field, providing a research tool for studying neural responses.

Extraordinary regeneration of neurons in zebrafish
Biologists from the University of Bayreuth have discovered a uniquely rapid form of regeneration in injured neurons and their function in the central nervous system of zebrafish.

Dopamine neurons mull over your options
Researchers at the University of Tsukuba have found that dopamine neurons in the brain can represent the decision-making process when making economic choices.

Neurons thrive even when malnourished
When animal, insect or human embryos grow in a malnourished environment, their developing nervous systems get first pick of any available nutrients so that new neurons can be made.

The first 3D map of the heart's neurons
An interdisciplinary research team establishes a new technological pipeline to build a 3D map of the neurons in the heart, revealing foundational insight into their role in heart attacks and other cardiac conditions.

Mapping the neurons of the rat heart in 3D
A team of researchers has developed a virtual 3D heart, digitally showcasing the heart's unique network of neurons for the first time.

How to put neurons into cages
Football-shaped microscale cages have been created using special laser technologies.

A molecule that directs neurons
A research team coordinated by the University of Trento studied a mass of brain cells, the habenula, linked to disorders like autism, schizophrenia and depression.

Read More: Neurons News and Neurons Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to