Garcia-Anoveros, Jaime, PhD



Garcia-Anoveros, Jaime, PhD


Associate Professor


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Departments of Anesthesiology, Physiology and Neurology Feinberg School of Medicine


Ward 10-070 Chicago


Areas of Research

Cell Biology, Molecular Neuroscience, Neurobiology of Disease, Signal Transduction

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Current Research

Current Research

Mechanotransduction, the process whereby a cell transforms a mechanical force into an electrochemical signal, underlies universal cellular processes such as volume regulation and cell motility. In addition, certain sensory cells are specialized in detecting mechanical forces: hair cells of the inner ear detect sounds and accelerations and allow us to hear and maintain balance; somatosensory neurons of the dorsal root and trigeminal ganglia detect deformations to the body and result in the perceptions of proprioception, touch and pain. Yet these are among the least understood senses, both at the physiological and at the molecular level.
A genetic dissection of touch in the nematode Caenorhabditis elegans led to the identification of proteins that mediate this sense in worms; these include structural components of the extracellular matrix and of the cytoskeleton, and membrane proteins called degenerins. I have demonstrated that degenerins form ion channels, and based on genetic analyses, have proposed a model whereby they connect to the cytoskeleton and extracellular matrix to become mechanically gated (Fig 1).

Figure 1. Macromolecular model of touch

More recently, I have found homologous proteins in mammals that form neuronal sodium channels that are not gated by voltage but instead may be opened by extracellular acidity (BNaC or ASIC). One of these channel proteins (BNaC1a) is expressed in touch-sensitive neurons (the large diameter neurons of the dorsal root and trigeminal ganglia), is transported from the cell bodies to the skin, and is located at specialized mechanosensory endings (Meissner, Merkel, penicillate, reticular, lanceolate, hair follicle palisades as well as A-d intraepidermal high-threshold mechanoreceptors; Fig 2). I suspect that the BNaC1a channel protein ñ like its homologs in nematode touch neurons ñ is a subunit of the macromolecular structures that mediate touch sensation in mammals. In addition, the sensitivity of BNaC channels to extracellular acidity, a known source of pain, may also implicate these channels in nociception.
Figure 2. BNaC1a in mechanosensory palisade endings around mouse hair follicles.

To identify and reconstitute all the proteins of these macromolecular complexes, we are searching for proteins that interact with BNaC1a through molecular, genomic and proteomic approaches. In collaboration with Dr. Anne Duggan, we have used a yeast two-hybrid screen to identify a protein that binds to the BNaC1a channel and that is present at touch-sensitive cutaneous terminals. To understand the role of these proteins we are also developing molecular and physiological tools to test their function in cutaneous sensation.
Finally, I found that some transcripts of these channels are widely expressed in brain neurons, and that one of the isoforms localizes to dendrites. We are working to elucidate the molecular mechanism by which BNaC1a is directionally targeted to the sensory terminals of DRG neurons as well as to the dendrites of CNS neurons. Although our primary focus is to study BNaC channels in the relatively simple context of mechanosensory and nociceptive terminals, the tools developed in the process will also aid in elucidating the physiological roles of these putative mechanosensitive and acid-sensitive channels in CNS neurons.