Within the cell, there are twomajor protein networks whose functions and interactions are critical for a large number of processes. These protein networks are the cytoskeleton localized in the cytoplasm and the nucleoskeleton present in the nucleus. They are separated by the nuclear envelope and, importantly, they are connected to each other through the linker of nucleoskeleton and cytoskeleton (LINC) complex embedded in the nuclear envelope. Together they play important roles not only in organization of cell structure and function but also in mechanotransduction and signaling pathways between the cytoplasm and nucleus and in regulation of transcription and gene expression. The cytoskeleton is a complex fibrous reticular structure which is functionally very diverse. It is composed of several types of cytoskeletal structures: actin filaments, microtubules (MTs), intermediate filaments (IFs), and spectrin. There is both a cortical cytoskeleton, localized just beneath the cell membrane, and a cytoplasmic cytoskeleton. The cortical cytoskeleton is comprised of a meshwork of actin filaments. Spectrin is associated with this actin network and links it to the cell membrane. The cortical cytoskeleton provides the cell membrane with structural stability, flexibility, and elasticity and plays an important role in membrane shape changes in response to external forces. The cytoplasmic cytoskeleton is composed not only of actin filaments, but also of MTs and IFs. Spectrin is also associated with these structures and with the surface of organelle membranes where it supplies them with stability and aids in their interactions as well. Cross-linking proteins, spectraplakins, are also involved in these interactions. The cytoplasmic cytoskeleton is important in intracellular transport, stabilization of the cell, and force transmission. Coordinated interactions between the cortical and cytoplasmic cytoskeletal proteins are essential for a number of cellular processes, including regulation of cell motility and migration, changes in cellular morphology, pinocytosis, endocytosis, cell adhesion, and signal transduction. Exciting new research on these proteins has demonstrated that they have additional and combined roles in mechanotransduction, movement of the nucleus during cell locomotion, cell adhesion and migration, and formation and functioning of the immune synapse. These cytoskeletal proteins form a dynamic and structured network that can respond to both internal and external signals and have the ability to reorganize as needed. Their interactions with each other are involved in many of the crucial regulatory aspects of cell function and in maintenance of cellular homeostasis. The importance of these proteins is evidenced in diseases in which loss, deficiency, or functional defects of a specific protein leads to physiological and pathophysiological consequences. The LINC complex, which spans the nuclear envelope, acts as a bridge to link the cytoskeleton to the nucleoskeleton. It has a critical function in transmitting forces generated in the cytoplasm to the structural elements of the nucleoskeleton, enabling communication of signals between the nucleus and cytoplasm. It also plays an important role in maintaining the architecture of the nuclear envelope. Protein components of the LINC complex associated with the inner nuclear membrane (INM) (SUN proteins) and the outer nuclear membrane (ONM) (KASH proteins) interact with nucleoskeletal proteins and cytoskeletal proteins, respectively, and are involved in a number of critical cellular functions which will be discussed in this thematic issue. Examinations of proteins associated with the nucleoskeleton have been more recent than those associated with the cytoskeleton, mainly due to technological advances in ability to identify these proteins in the nucleus. There is both a peripheral and an internal nucleoskeleton. The peripheral nucleoskeleton lies in the periphery of the nucleus along the inner membrane of the nuclear envelope. It is composed of the nuclear lamina, which is a complex network of nuclear lamins and associated proteins which include actin, nuclear myosin, emerin, titian, and spectrin. It provides a structural framework for support of the nuclear membrane and nuclear architecture. The peripheral nucleoskeleton also provides a platform for interactions with other functionally important nuclear

Journal of the European Academy of Dermatology and VenereologyVolume 32, Issue 5 p. e202-e204 Letter to the Editor How sildenafil (Viagra®) may cause melanoma: a histopathologic study providing a potential physiological/etiopathological mechanism W.C. Lambert, Corresponding Author W.C. Lambert lamberwc@njms.rutgers.edu New Jersey Medical School, Department of Dermatology and Pathology and Laboratory Medicine, Rutgers University, Newark, NJ, USACorrespondence: W.C. Lambert E-mail: lamberwc@njms.rutgers.eduSearch for more papers by this authorM.W. Lambert, M.W. Lambert New Jersey Medical School, Department of Dermatology and Pathology and Laboratory Medicine, Rutgers University, Newark, NJ, USASearch for more papers by this authorC.M. Ring, C.M. Ring New Jersey Medical School, Department of Dermatology and Pathology and Laboratory Medicine, Rutgers University, Newark, NJ, USASearch for more papers by this authorC.E. Gagna, C.E. Gagna Department of Life Sciences, New York Institute of Technology, Old Westbury, NY, USASearch for more papers by this authorJ.D. Espinal-Mariotte, J.D. Espinal-Mariotte New Jersey Medical School, Department of Dermatology and Pathology and Laboratory Medicine, Rutgers University, Newark, NJ, USASearch for more papers by this authorR.A. Schwartz, R.A. Schwartz New Jersey Medical School, Department of Dermatology and Pathology and Laboratory Medicine, Rutgers University, Newark, NJ, USASearch for more papers by this author W.C. Lambert, Corresponding Author W.C. Lambert lamberwc@njms.rutgers.edu New Jersey Medical School, Department of Dermatology and Pathology and Laboratory Medicine, Rutgers University, Newark, NJ, USACorrespondence: W.C. Lambert E-mail: lamberwc@njms.rutgers.eduSearch for more papers by this authorM.W. Lambert, M.W. Lambert New Jersey Medical School, Department of Dermatology and Pathology and Laboratory Medicine, Rutgers University, Newark, NJ, USASearch for more papers by this authorC.M. Ring, C.M. Ring New Jersey Medical School, Department of Dermatology and Pathology and Laboratory Medicine, Rutgers University, Newark, NJ, USASearch for more papers by this authorC.E. Gagna, C.E. Gagna Department of Life Sciences, New York Institute of Technology, Old Westbury, NY, USASearch for more papers by this authorJ.D. Espinal-Mariotte, J.D. Espinal-Mariotte New Jersey Medical School, Department of Dermatology and Pathology and Laboratory Medicine, Rutgers University, Newark, NJ, USASearch for more papers by this authorR.A. Schwartz, R.A. Schwartz New Jersey Medical School, Department of Dermatology and Pathology and Laboratory Medicine, Rutgers University, Newark, NJ, USASearch for more papers by this author First published: 01 December 2017 https://doi.org/10.1111/jdv.14723Citations: 4 All authors contributed equally. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume32, Issue5May 2018Pages e202-e204 RelatedInformation