The external surfaces of the human body, as well as its internal organs, constantly experience different kinds of mechanical stimulations. For example, tubular epithelial cells of the kidney are continuously exposed to a variety of mechanical forces, such as fluid flow shear stress within the lumen of th nephron. The majority of epithelial cells along the nephron, except intercalated cells, possess a primary cilium, an organelle projecting from the cell's apical surface into the luminal space. Despite its discovery over 100 (...) years ago, the primary cilium's function continued to elude researchers for many decades. However, recent studies indicate that renal cilia have a sensory function. Studies on polycystic kidney disease (PKD) have identified many of the molecular players, which should help solve the mystery of how the renal cilium senses fluid flow. In this review, we will summarize the recent breakthroughs in PKD research and discuss the role(s) of th polycystin signaling complex in mediating mechanosensory function by the primary cilium of renal epithelium as well as of the embryonic node. BioEssays 26:844–856, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Chemosensation and mechanosensation cover an enormous spectrum of processes by which animals use information from the environment to adapt their behavior. For pragmatic reasons, these sensory modalities are commonly investigated independently. Recent advances, however, have revealed numerous situations in which they function together to control animals’ actions. Highlighting examples from diverse vertebrates and invertebrates, we first discuss sensory receptors and neurons that have dual roles in the detection of chemical and mechanical stimuli. Next we present cases where peripheral chemosensory and (...) mechanosensory pathways are discrete but intimately packaged to permit coordinated reception of external cues. Finally, we consider how chemical and mechanical signals converge in central neural circuitry to enable multisensory integration. These insights demonstrate how investigation of the interplay between different sensory modalities is key to a more holistic and realistic understanding of sensory‐guided behaviors. (shrink)

The nematode C. elegans exhibits a variety of reponses to touch. When specific sets of mechanosensory neurons are killed with a laser, specific touch responses are abolished. Many mutations that result in defective mechanosensation have been identified. Some of the mutations define genes that specify the fate of a set of mechanoreceptors called the touch cells, which mediate response to light touch to the body of the worm. Genes specifying touch cell fate appear to regulate genes that encode touch‐cell differentiation (...) proteins, including apparent subunits of a touch‐cell‐specific ion channel, rare mutant forms of which lead to swelling and lysis of the touch cells. Molecular attachments of the ion channel, both to extracellular matrix components and, intracellularly, to a special large‐diameter microtubule, may be required for mechanical gating of the channel. A mechanoreceptor‐interneuron‐motorneuron reflex circuit for response to light touch has been proposed. (shrink)

Mechanical pain sensing, adipogenesis, and STING‐dependent innate immunity seem three distinct biological processes without substantial relationships. Intriguingly, TMEM120A, a transmembrane protein, has been shown to detect mechanical pain stimuli as a mechanosensitive channel, contribute to adipocyte differentiation/function by regulating genome organization and promote STING trafficking to active cellular innate immune response. However, the role of TMEM120A as a mechanosensitive channel was challenged by recent studies which cannot reproduce data supporting its role in mechanosensing. Furthermore, the molecular mechanism by which (...) TMEM120A contributes to adipocyte differentiation/function and promotes STING trafficking remains elusive. In this review, we discuss these multiple proposed functions of TMEM120A and hypothesize the molecular mechanism underlying TMEM120A's role in fatty acid metabolism and STING signaling. (shrink)

The YAP/TAZ family of transcriptional co‐activators drives cell proliferation in epithelial tissues and cancers. Yet, how YAP and TAZ are physiologically regulated remains unclear. Here we review recent reports that YAP and TAZ act primarily as sensors of epithelial cell polarity, being inhibited when cells differentiate an apical membrane domain, and being activated when cells contact the extracellular matrix via their basal membrane domain. Apical signalling occurs via the canonical Crumbs/CRB‐Hippo/MST‐Warts/LATS kinase cascade to phosphorylate and inhibit YAP/TAZ. Basal signalling occurs (...) via Integrins and Src family kinases to phosphorylate and activate YAP/TAZ. Thus, YAP/TAZ is localised to the nucleus in basal stem/progenitor cells and cytoplasm in differentiated squamous cells or columnar cells. In addition, other signals such as mechanical forces, tissue damage and possibly receptor tyrosine kinases (RTKs) can influence MST‐LATS or Src family kinase activity to modulate YAP/TAZ activity. (shrink)

The sense of touch informs us of the physical properties of our surroundings and is a critical aspect of communication. Before touches are perceived, mechanical signals are transmitted quickly and reliably from the skin's surface to mechano‐electrical transduction channels embedded within specialized sensory neurons. We are just beginning to understand how soft tissues participate in force transmission and how they are deformed. Here, we review empirical and theoretical studies of single molecules and molecular ensembles thought to be involved in mechanotransmission (...) and apply the concepts emerging from this work to the sense of touch. We focus on the nematode Caenorhabditis elegans as a well‐studied model for touch sensation in which mechanics can be studied on the molecular, cellular, and systems level. Finally, we conclude that force transmission is an emergent property of macromolecular cellular structures that mutually stabilize one another. (shrink)