Endocytosis and Signaling: Cell Logistics Shape the Eukaryotic Cell Plan

Abstract

<jats:p>Our understanding of endocytosis has evolved remarkably in little more than a decade. This is the result not only of advances in our knowledge of its molecular and biological workings, but also of a true paradigm shift in our understanding of what really constitutes endocytosis and of its role in homeostasis. Although endocytosis was initially discovered and studied as a relatively simple process to transport molecules across the plasma membrane, it was subsequently found to be inextricably linked with almost all aspects of cellular signaling. This led to the notion that endocytosis is actually the master organizer of cellular signaling, providing the cell with understandable messages that have been resolved in space and time. In essence, endocytosis provides the communications and supply routes (the logistics) of the cell. Although this may seem revolutionary, it is still likely to be only a small part of the entire story. A wealth of new evidence is uncovering the surprisingly pervasive nature of endocytosis in essentially all aspects of cellular regulation. In addition, many newly discovered functions of endocytic proteins are not immediately interpretable within the classical view of endocytosis. A possible framework, to rationalize all this new knowledge, requires us to “upgrade” our vision of endocytosis. By combining the analysis of biochemical, biological, and evolutionary evidence, we propose herein that endocytosis constitutes one of the major enabling conditions that in the history of life permitted the development of a higher level of organization, leading to the actuation of the eukaryotic cell plan.</jats:p>

Tyrosine 1045 Codon Mutations in Exon 27 of EGFR are Infrequent in Oral Squamous Cell Carcinomas

“…The finding also carries clinical significance as glioblastomas carrying a deletion mutant of EGFR -EGFRvIII, which has an in-frame deletion in its cytoplasmic domain, are either hypophosphorylated or not phosphorylated at tyrosine resistant 1045 (Sigismund et al, 2012), are not degraded upon treatment with tyrosine kinase inhibitors and are resistant to the EGFR inhibitor drug, gefitinib (Sigismund et al, 2012). As the usage of several EGFR inhibitor drugs are in clinical trials for therapeutic management of OSCCs (El-Rayes et al, 2004), the absence of mutation at tyrosine 1045 codon suggests that OSCCs may respond favorably to therapeutic management.…”

Endocytic Accessory Factors and Regulation of Clathrin-Mediated Endocytosis

“…Many of these more recent studies have exploited advances in fluorescence microscopy and the use of fluorescent proteins (FPs) in live-cell imaging. We do not discuss the relationship between receptor-mediated endocytosis and signaling, which has been covered by recent reviews (Sigismund et al 2012; see also Bökel and Brand 2013;Cosker and Segal 2014;Di Fiore and von Zastrow 2014).…”

A Novel Heterozygous Mutation (F252Y) in Exon 7 of the IRF6 Gene is Associated with Oral Squamous Cell Carcinomas

“…While these studies clearly highlight the emerging importance of the components of interferon pathway in the development and treatment of carcinomas, it becomes critical to note that our finding of a mutation in IRF6 carries significant clinical value as incidence of resistance of cancer cells to chemotherapeutic agents have been reported especially in cells carrying mutant genes. For example, cancer cells expressing mutant epidermal growth factor receptor (EGFR) molecules have been found to be resistant to chemotherapeutic drugs (Sigismund et al, 2012). Hence it is possible that the F252Y mutation identified in the three OSCCs in the present study may be expected to confer resistance to chemotherapeutic drugs as well.…”