The sense of touch is vital for our survival, as it is essential for purposes as simple as picking up a fork and as complex as bonding with a newborn. Despite its importance for accomplishing basic tasks, the molecular and cellular mechanisms that convert a force on the skin into a neural signal are poorly understood. The long term goal of this research is to elucidate how receptors in the skin convert a touch stimulus into a neural signal to inform our brains about the physical world. We use Merkel cell-neurite complexes, which are conserved discriminative touch receptors, as a model to study these processes. Merkel cells are epithelial derived target cells that contact the endings of sensory neurons that send information to the central nervous system. Stimulating these Merkel cell-neurite complexes generates slowly adapting type I responses, which are important for detecting object features such as edges and curvature. Our previous studies revealed that Merkel cells directly sense mechanical force and convey this information to the underlying sensory neurons. The molecules that govern this process are completely unknown. Numerous molecules involved in synaptic transmission and neurotransmitters have been identified in Merkel cells, yet attempts to identify signaling mechanisms in vivo have yielded contradictory results. Thus, the objective of this research is to identify mechanisms by which Merkel cells convey tactile information to the nervous system. We will accomplish this goal by using an innovative combination of transgenic mice, optogenetics, in vitro and ex vivo physiology, and behavioral studies. Our central hypothesis is that Merkel cells release neurotransmitters at TeNT-sensitive SNARE-dependent chemical synapses to excite firing in tactile afferents.
In Aim 1, we will determine whether Merkel cells employ TeNT-sensitive SNARE-mediated vesicular release.
Aim 2 will identify the neurotransmitter or neuromodulatory pathways that excite Merkel-cell afferent neurons. These studies will yield fundamental insights into peripheral tactile mechanisms, which is essential to advance basic knowledge of principles that govern encoding of somatic senses.
The sense of touch is essential for fundamental tasks such as grasping objects, social bonding and navigating the world around us, yet little is known about the cellular processes that generate touch signals. We will analyze the mechanisms by which Merkel cell-neurite complexes, important touch receptors that reside in the skin, convert touch stimuli into neuronal signals to inform the brain about objects in our environment. This research will provide important insights into basic sensory processes and the interaction between the skin and nervous system
| Hill, Rose Z; Hoffman, Benjamin U; Morita, Takeshi et al. (2018) The signaling lipid sphingosine 1-phosphate regulates mechanical pain. Elife 7: |
| Moayedi, Yalda; Duenas-Bianchi, Lucia F; Lumpkin, Ellen A (2018) Somatosensory innervation of the oral mucosa of adult and aging mice. Sci Rep 8:9975 |
| Jenkins, Blair A; Lumpkin, Ellen A (2017) Developing a sense of touch. Development 144:4078-4090 |
| Nakatani, Masashi; Maksimovic, Srdjan; Baba, Yoshichika et al. (2015) Mechanotransduction in epidermal Merkel cells. Pflugers Arch 467:101-8 |
| Woo, Seung-Hyun; Lumpkin, Ellen A; Patapoutian, Ardem (2015) Merkel cells and neurons keep in touch. Trends Cell Biol 25:74-81 |
| Walsh, Carolyn M; Bautista, Diana M; Lumpkin, Ellen A (2015) Mammalian touch catches up. Curr Opin Neurobiol 34:133-9 |
| Woo, Seung-Hyun; Ranade, Sanjeev; Weyer, Andy D et al. (2014) Piezo2 is required for Merkel-cell mechanotransduction. Nature 509:622-6 |
| Maksimovic, Srdjan; Nakatani, Masashi; Baba, Yoshichika et al. (2014) Epidermal Merkel cells are mechanosensory cells that tune mammalian touch receptors. Nature 509:617-21 |
| Owens, David M; Lumpkin, Ellen A (2014) Diversification and specialization of touch receptors in skin. Cold Spring Harb Perspect Med 4: |
| Wilson, Sarah R; Nelson, Aislyn M; Batia, Lyn et al. (2013) The ion channel TRPA1 is required for chronic itch. J Neurosci 33:9283-94 |
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