Molecular profiling reveals synaptic release machinery in Merkel cells

Haeberle, Henry; Fujiwara, Mika; Chuang, Jody C.; Medina, Michael M.; Panditrao, Mayuri V.; Bechstedt, Susanne; Howard, Jonathon; Lumpkin, Ellen A.

doi:10.1073/pnas.0406308101

Cited by 159 publications

(208 citation statements)

References 54 publications

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“…A favored model is that, by analogy to hair cells, mechanical deformation of Merkel cell microvilli initiates Ca 2+ influx and a signaling cascade that results in neurotransmitter release onto the affiliated neurite. In support of this model, Merkel cells are excitable, contain small dense-core and clear vesicles and are enriched in key presynaptic proteins and neurotransmitters [53,54]. Interestingly, a mechanosensory function has also been postulated for another class of cells with espin-containing microvilli: epithelial cells in renal proximal tubule [12].…”

Section: Espins In the Microvillar Processes Of Other Sensory Cellsmentioning

confidence: 92%

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Espins and the actin cytoskeleton of hair cell stereocilia and sensory cell microvilli

Sekerková

Zheng

Loomis

et al. 2006

Cell. Mol. Life Sci.

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The espins are novel actin-bundling proteins that are produced in multiple isoforms from a single gene. They are present at high concentration in the parallel actin bundle of hair cell stereocilia and are the target of deafness mutations in mice and humans. Espins are also enriched in the microvilli of taste receptor cells, solitary chemoreceptor cells, vomeronasal sensory neurons and Merkel cells, suggesting that espins play important roles in the microvillar projections of vertebrate sensory cells. Espins are potent actin-bundling proteins that are not inhibited by Ca 2+ . In cells, they efficiently elongate parallel actin bundles and, thereby, help determine the steady-state length of microvilli and stereocilia. Espins bind actin monomer via their WH2 domain and can assemble actin bundles in cells. Certain espin isoforms can also bind phosphatidylinositol 4,5-bisphosphate, profilins or SH3 proteins. These biological activities distinguish espins from other actin-bundling proteins and may make them well-suited to sensory cells. KeywordsEspin; actin; hair cell; stereocilia; microvilli; sensory; deafness; taste The stereocilia and microvilli of vertebrate sensory cells and their actinbundling proteinsMany classes of vertebrate sensory cells detect chemical or mechanical stimuli through microvilli or their derivatives, such as stereocilia. These relatively long-lived, fingerlike specializations of the plasma membrane are built around a common cytoskeletal element -the parallel actin bundle (PAB) [1]. PABs consist of tightly packed collections of actin filaments cross-linked by actin-bundling proteins. The filaments are aligned along their longitudinal axis and display a uniform polarity with respect to their preferred ends for actin monomer addition, which in microvilli and stereocilia is positioned at the distal tip. The PAB displays hallmarks of a supramolecular scaffold that determines the placement, dimensions, flexibility and signaling properties of microvilli and stereocilia. Although filopodia also contain a PAB at their core and are believed to sense the local environment, they are considerably more dynamic and differ significantly from microvilli and stereocilia in their molecular composition and biogenesis [2].

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Section: Espins In the Microvillar Processes Of Other Sensory Cellsmentioning

confidence: 92%

“…Merkel cells display the properties of mechanoreceptors [53,54]. They are found in a complex with enlarged terminal endings of nerve fibers and are believed to be sensitive touch receptors.…”

Section: Espins In the Microvillar Processes Of Other Sensory Cellsmentioning

confidence: 99%

Espins and the actin cytoskeleton of hair cell stereocilia and sensory cell microvilli

Sekerková

Zheng

Loomis

et al. 2006

Cell. Mol. Life Sci.

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“…Different transcription factors known to regulate cell fate specification such as Lhx3, Atoh1/Math1, Mash1, or Islet1 are preferentially expressed in neonatal mouse MCs (Haeberle et al, 2004). Atoh1/Math1 is expressed in developing and adult MCs (Ben-Arie et al, 2000;Lumpkin et al, 2003;Haeberle et al, 2004) and in embryonic P-cadherinpositive hair progenitor cells (Rhee et al, 2006).…”

Section: Conditional Deletion Of Atoh1 In Embryonic Epidermal Progenimentioning

confidence: 99%

“…MCs are clustered in touch-sensitive zones of the glabrous and hairy skin, called touch domes, and are densely innervated by slowly adapting type I mechanoreceptor nerve fibers. MCs express intermediate filaments of primitive and simple epithelia such as keratin 8 (K8), K18, or K20 but also express neuropeptides and many components of the presynaptic machinery such as synaptotagmin or Rab3c and transcription factors involved in neuronal cell fate determination (Haeberle et al, 2004). An electrophysiological study demonstrated that MCs are excitable cells (Yamashita et al, 1992) that express voltagegated channels, inducing calcium influx in response to depolarization (Haeberle et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

“…MCs express intermediate filaments of primitive and simple epithelia such as keratin 8 (K8), K18, or K20 but also express neuropeptides and many components of the presynaptic machinery such as synaptotagmin or Rab3c and transcription factors involved in neuronal cell fate determination (Haeberle et al, 2004). An electrophysiological study demonstrated that MCs are excitable cells (Yamashita et al, 1992) that express voltagegated channels, inducing calcium influx in response to depolarization (Haeberle et al, 2004). Selective destruction of MCs by photoablation (Ikeda et al, 1994) or their loss in mice genetically deficient for MCs (Maricich et al, 2009) abolishes responses of slowly adapting type I mechanoreceptor units, which is consistent with the requirement of MCs to mediate slow adapting mechanotransduction in the skin.…”

Section: Introductionmentioning

confidence: 99%

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Epidermal progenitors give rise to Merkel cells during embryonic development and adult homeostasis

Keymeulen¹,

Mascré²,

Youseff³

et al. 2009

J Exp Med

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Keratinocytes Communicate with Sensory Neurons via Synaptic‐like Contacts

Talagas

Lebonvallet

Leschiera

et al. 2020

Annals of Neurology

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Objective: Pain, temperature, and itch are conventionally thought to be exclusively transduced by the intraepidermal nerve endings. Although recent studies have shown that epidermal keratinocytes also participate in sensory transduction, the mechanism underlying keratinocyte communication with intraepidermal nerve endings remains poorly understood. We sought to demonstrate the synaptic character of the contacts between keratinocytes and sensory neurons and their involvement in sensory communication between keratinocytes and sensory neurons. Methods: Contacts were explored by morphological, molecular, and functional approaches in cocultures of epidermal keratinocytes and sensory neurons. To interrogate whether structures observed in vitro were also present in the human epidermis, in situ correlative light electron microscopy was performed on human skin biopsies. Results: Epidermal keratinocytes dialogue with sensory neurons through en passant synaptic-like contacts. These contacts have the ultrastructural features and molecular hallmarks of chemical synaptic-like contacts: narrow intercellular cleft, keratinocyte synaptic vesicles expressing synaptophysin and synaptotagmin 1, and sensory information transmitted from keratinocytes to sensory neurons through SNARE-mediated (syntaxin1) vesicle release. Interpretation: By providing selective communication between keratinocytes and sensory neurons, synaptic-like contacts are the hubs of a 2-site receptor. The permanent epidermal turnover, implying a specific en passant structure and high plasticity, may have delayed their identification, thereby contributing to the long-held concept of nerve endings passing freely between keratinocytes. The discovery of keratinocyte-sensory neuron synaptic-like contacts may call for a reassessment of basic assumptions in cutaneous sensory perception and sheds new light on the pathophysiology of pain and itch as well as the physiology of touch.

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Molecular profiling reveals synaptic release machinery in Merkel cells

Cited by 159 publications

References 54 publications

Espins and the actin cytoskeleton of hair cell stereocilia and sensory cell microvilli

Espins and the actin cytoskeleton of hair cell stereocilia and sensory cell microvilli

Epidermal progenitors give rise to Merkel cells during embryonic development and adult homeostasis

Keratinocytes Communicate with Sensory Neurons via Synaptic‐like Contacts

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