Memory formation and the regulation of gene expression

On a cellular level, formation of memory is based on a selective change in synaptic efficacy that is both fast and, in case of important information, long-lasting. Rapidity of cellular changes is achieved by modifying preexisting synaptic molecules (receptors, ion channels), which instantaneously alters the efficacy of synaptic transmission. Endurance, that is the formation of long-term memory (LTM), is based on transient and perhaps also long-lasting changes in protein synthesis. A number of different methods exist to interfere with the synthesis of specific proteins or proteins in general. Other methods, in turn, help to identify proteins whose synthesis is changed following learning. These mostly molecular methods are briefly described in the present review. Their successful application in a variety of memory paradigms in invertebrates and vertebrates is illustrated. The data support the importance of selective changes in gene expression for LTM. Proteins newly synthesized during memory consolidation are likely to contribute to restructuring processes at the synapse, altering the efficiency of transmission beyond the scope of STM. Increased or, less often, decreased synthesis of proteins appears during specific time windows following learning. Recent evidence supports older data suggesting that two or even more waves of protein synthesis exist during the consolidation period. It is expected that the new molecular methods will help to identify and characterize molecules whose expression changes during LTM formation even in complex vertebrate learning paradigms.     

Leukocyte integrins and inflammation

Leukocyte adhesion is of pivotal functional importance. Without adequate adhesion, T lymphocytes and natural killer cells are not cytotoxic, B cells cannot develop into antibody secreting plasma cells, leukocytes do not home into inflamed tissues and myeloid cells are not able to phagocytize or exhibit chemotactic responses. During evolution several leukocyte adhesion molecules have developed belonging to a few molecular families. Among these, the leukocyte-specific integrins (β ₂ integrins, CD11/CD18 molecules) are among the most important. Much progress has taken place during the past few years, and at present we have a considerable knowledge of their structure and function. Inflammation is critically dependent on integrin activity, and its regulation forms the topic of this short review.     

MAP kinases in plant signal transduction

Mitogen-activated protein kinase (MAPK) pathways are modules involved in the transduction of extracellular signals to intracellular targets in all eukaryotes. Distinct MAPK pathways are regulated by different extracellular stimuli and are implicated in a wide variety of biological processes. In plants there is evidence for MAPKs playing a role in the signaling of abiotic stresses, pathogens and plant hormones. The large number and divergence of plant MAPKs indicates that this ancient mechanism of bioinformatics is extensively used in plants and may provide a new molecular handle on old questions.     

The Janus kinase family of protein tyrosine kinases and their role in signaling

In the early 1990s, the search for protein kinases led to the discovery of a novel family of non-receptor tyrosine kinases, the Janus kinases or JAKs. These proteins were unusual because they contained two kinase homology domains and no other known signaling modules. It soon became clear that these were not ‘just another’ type of kinase. Their ability to complement mutant cells insensitive to interferons and to be activated by a variety of cytokines demonstrated their central signaling function. Now, as we approach the end of the decade, it is evident from biochemical studies to knockout mice that JAKs play non-redundant functions in development, differentiation, and host defense mechanisms. Here, recent progress is reviewed, with particular emphasis on structure-function studies aimed at revealing how this family of tyrosine kinases is regulated.     

Revisiting retinoblastoma protein phosphorylation during the mammalian cell cycle

It is widely accepted that phosphorylation of the retinoblastoma (Rb) protein during the G1 phase of the mammalian division cycle is a major control element regulating passage of cells into S phase and through the division cycle. The experiments supporting G1-phase-specific Rb phosphorylation and the historical development of this idea are reviewed. By making a rigorous distinction between 'growth cessation' and the phenomena of 'cell cycle exit' or 'G1-phase arrest', the evidence for the G1-phase-specific phosphorylation of Rb protein is reinterpreted. We show that the evidence for G1-phase phosphorylation of Rb rests on few experiments and a chain of reasoning with some weak links. Evidence is reviewed that growth conditions regulate the phosphorylation of Rb. A growth-regulated control system that is independent of the cell cycle explains much of the evidence adduced to support cycle-specific phosphorylation of Rb. We propose that additional experimental evidence is needed to decide whether there is a G1-phase-specific phosphorylation of Rb protein. Received 16 October 2000; received after revision 13 November 2000; accepted 15 November 2000