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- Trends Cell Biol 19(6):i (2009)
- Unconventional myosins acting unconventionally
- Trends Cell Biol 19(6):245-252 (2009)
Unconventional myosins are proteins that bind actin filaments in an ATP-regulated manner. Because of their association with membranes, they have traditionally been viewed as motors that function primarily to transport membranous organelles along actin filaments. Recently, however, a wealth of roles for myosins that are not obviously related to organelle transport have been uncovered, including organization of F-actin, mitotic spindle regulation and gene transcription. Furthermore, it has also become apparent that the motor domains of different myosins vary strikingly in their biophysical attributes. We suggest that the assumption that most unconventional myosins function primarily as organelle transporters might be misguided. - Endoplasmic and sarcoplasmic reticulum in the heart
- Trends Cell Biol 19(6):253-259 (2009)
The concept of the presence of sarcoplasmic reticulum (SR) membrane in the heart is widely accepted and has been considered merely to be a different name for the endoplasmic reticulum (ER) in muscle tissues. Cardiac SR membranes are specialized in the regulation of Ca2+ transport and control of excitation–contraction coupling. By contrast, the ER is responsible for protein synthesis, modification, secretion, lipid and steroid synthesis, and modulation of Ca2+ signaling. Recent developments have indicated that functional changes in proteins or pathways normally associated with ER and not SR membrane impact cardiac development and pathology. Here, we propose that the SR and ER might be functionally distinct internal membrane compartments in cardiomyocytes. - Nutrient control of TORC1, a cell-cycle regulator
- Trends Cell Biol 19(6):260-267 (2009)
It is well established that the target of rapamycin (TOR) protein kinase has pivotal roles in controlling cell functions (including protein synthesis, cell growth and cell proliferation) and is implicated in numerous human diseases. Mammalian TOR complex 1 (mTORC1) signalling is activated by hormones and growth factors, and is also stimulated by intracellular amino acids. Recent research has provided important new insight into the poorly understood mechanism by which amino acids activate mTORC1 signalling, showing that the protein kinase MAP4K3 and Rag GTPases have important roles in this. mTORC1 is known to control the G1/S transition of the cell cycle: new data show that (m)TORC1 also controls G2/M progression in yeast and mammals, albeit in contrasting ways. - Regeneration, repair and remembering identity: the three Rs of Hox gene expression
- Trends Cell Biol 19(6):268-275 (2009)
Hox genes encode transcription factors that specify embryonic positional identity in cells and guide tissue differentiation. Recent advances have greatly increased our understanding of the epigenetic mechanisms that ensure the faithful expression of Hox genes in adult cells and which involve the interplay of histone methylation, demethylation and intergenic transcription of long non-coding RNAs. The transcriptional memory of Hox genes poses both an opportunity and a challenge for regenerative medicine. Matching the positional identity of transplanted stem cells with that of the host environment, as reflected by their respective Hox profiles, is likely to be required to achieve regenerative healing. Strategies to manipulate the plasticity of Hox gene expression will probably become a major focus in regenerative medicine. - New players in actin polymerization – WH2-domain-containing actin nucleators
- Trends Cell Biol 19(6):276-285 (2009)
Actin nucleators promote the polymerization of the different types of actin arrays formed in a variety of cellular processes, such as cell migration, cellular morphogenesis and membrane trafficking processes. Several novel nucleators have been discovered recently. They all contain Wiskott-Aldrich syndrome protein (WASP) homology 2 (WH2 or W) domains for actin nucleation but seem to employ different molecular mechanisms and serve distinct cellular functions. Here, we summarize what is currently known about the different molecular mechanisms that Spire, Cordon-Bleu and Leiomodin seem to use and, also, the bacterial counterparts that mimic them (VopF, VopL and TARP). Recent studies on these WH2 proteins offer unique insight into the biological problem of actin-filament formation and how cells use specialized molecular machines to bring about so many different cytoskeletal structures. - Chromatin: the interface between extrinsic cues and the epigenetic regulation of muscle regeneration
- Trends Cell Biol 19(6):286-294 (2009)
Muscle regeneration provides a paradigm by which to study how extrinsic signals coordinate gene expression in somatic stem cells (satellite cells) by directing the genome distribution of chromatin-modifying complexes. Understanding the signal-dependent control of the epigenetic events underlying the transition of muscle stem cells through sequential regeneration stages holds the promise to reveal new targets for selective interventions toward repairing diseased muscles. This review describes the latest findings on how regeneration cues are integrated at the chromatin level to build the transcription network that regulates progression of endogenous muscle progenitors throughout the myogenic program. In particular, we describe how specific epigenetic signatures can confer responsiveness to extrinsic cues on discrete regions of the muscle stem cell genome.
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