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Biomedical subjects

Lynne Chang

Publications and source records attributed to Lynne Chang.

4 recordsLinked to original sources

Assembling an intermediate filament network by dynamic cotranslation.

We have been able to observe the dynamic interactions between a specific messenger RNA (mRNA) and its protein product in vivo by studying the synthesis and assembly of peripherin intermediate filaments (IFs). The results show that peripherin mRNA-containing particles (messenger ribonucleoproteins [mRNPs]) move mainly along microtubules (MT). These mRNPs are translationally silent, initiating translation when they cease moving. Many peripherin mRNPs contain multiple mRNAs, possibly amplifying the total amount of protein synthesized within these "translation factories." This mRNA clustering is dependent on MT, regulatory sequences within the RNA and the nascent protein. Peripherin is cotranslationally assembled into insoluble, nonfilamentous particles that are precursors to the long IF that form extensive cytoskeletal networks. The results show that the motility and targeting of peripherin mRNPs, their translational control, and the assembly of an IF cytoskeletal system are linked together in a process we have termed dynamic cotranslation.

Animals↗

Intermediate filaments are dynamic and motile elements of cellular architecture.

Recent evidence showing that intermediate filaments (IFs) are dynamic, motile elements of the cytoskeletal repertoire of vertebrate cells has overturned the long-standing view that they simply form static 'space filling' cytoplasmic networks. In fact, many types of IF are now known to engage in a remarkable array of movements that are closely associated with their assembly, disassembly and subcellular organization. Some of these motile properties are intrinsic to IFs and others are attributable to molecular crosstalk with either microtubules or actin-containing microfilaments. This crosstalk is, to a large extent, mediated by molecular motors, including conventional kinesin and cytoplasmic dynein. These motors are responsible for the high-speed delivery of nonfilamentous IF precursors and short filaments to specific regions of the cytoplasm, where they assemble into long IFs. Interestingly, the patterns and speeds of IF movements vary in different cell types and even within different regions of the same cell. These differences in motility may be related to their interactions with different types of molecular motor and/or other factors, such as IF-associated proteins.

Actin Cytoskeleton↗

Intermediate filaments mediate cytoskeletal crosstalk.

Intermediate filaments, actin-containing microfilaments and microtubules are the three main cytoskeletal systems of vertebrate and many invertebrate cells. Although these systems are composed of distinctly different proteins, they are in constant and intimate communication with one another. Understanding the molecular basis of this cytoskeletal crosstalk is essential for determining the mechanisms that underlie many cell-biological phenomena. Recent studies have revealed that intermediate filaments and their associated proteins are important components in mediating this crosstalk.

Actin Cytoskeleton↗

The dynamic and motile properties of intermediate filaments.

For many years, cytoplasmic intermediate filaments (IFs) were considered to be stable cytoskeletal elements contributing primarily to the maintenance of the structural and mechanical integrity of cells. However, recent studies of living cells have revealed that IFs and their precursors possess a remarkably wide array of dynamic and motile properties. These properties are in large part due to interactions with molecular motors such as conventional kinesin, cytoplasmic dynein, and myosin. The association between IFs and motors appears to account for much of the well-documented molecular cross talk between IFs and the other major cytoskeletal elements, microtubules, and actin-containing microfilaments. Furthermore, the associations with molecular motors are also responsible for the high-speed, targeted delivery of nonfilamentous IF protein cargo to specific regions of the cytoplasm where they polymerize into IFs. This review considers the functional implications of the motile properties of IFs and discusses the potential relationships between malfunctions in these motile activities and human diseases.

Animals↗