Introduction: Intercellular signals and the cytoskeleton
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Introduction: Intercellular signals and the cytoskeleton Jesús Avila THANKS TO THE pioneering studies of Hamburger and Levi-Montalcini (J Exp Zool 111: 457) it is now clear that some cells require the secreted products from other cells in order to survive. Indeed Raff and colleagues (Science 262: 695) have recently suggested that probably all mammalian cells, except blasto- meres, need extracellular signals (produced by other cells) for survival. Extracellular signals also make cells proliferate or differentiate. In the first case, dividing cells undergo replicative senescence after a limited number of cell cycles (Campisi, Cell 84: 497). When the cells differentiate, they could adhere to each other, thus giving rise to the formation of tissues and organs. Thus, an increase in the search for survival, proliferation or differentiation factors has occurred in the last decade (see for example the issue edited by L. Gillespie on Growth Factors in Development in Semin Dev Biol, 1991). This study has been mainly comple- mented with the analysis of the receptor molecules present in the target cells. The activation of these receptors usually results in the modification of certain enzymes like protein kinases involved in signal trans- duction inside the cell (some aspects of this topic have also been reviewed in Semin Cell Biol). One of the major consequences of signal transduc- tion is the development of cell morphological changes. The structure responsible for these changes is the cytoskeleton. Thus, it seems very important to determine the mechanism explaining how an extrac- ellular signal induces cytoskeletal rearrangements. In the cases of cell–cell interaction, surface proteins of the two cells could interact with each other and trigger an intracellular signal that modifies the cytoskeleton, thus determining the morphology of the tissue, as discussed by Gumbiner (Cell 84: 345). The objective of the present set of reviews is the analysis of the different steps that take place from receiving an extracellular signal to the modification of the cytoskeleton. Thus, specific examples of the relationship between signal transduction and the three elements of the cytoskeleton: microfilaments, intermediate filaments and microtubules are indi- cated. Another purpose of this issue is to discuss the generality of these interactions in different cell types. The occurrence of the pathway: extracellular signal → membrane receptors → cytoskeletal rearrangement → morphological changes, will be a recurrent topic throughout the present reviews. In some cases, the reception of an extracellular signal activates phospholipase C γ that acts on phosphoinositides to which membrane-actin binding proteins like profilin are bound. This results in changes in the level of actin polymerization. It is also known that some extracellular signals may activate GTP-binding proteins like Rho, Rac and Cdc 42 which promote changes in microfilament organization. In particular, Rho protein seems to be involved in the changes elicited by extracellular matrix components through their binding to integrins. On the other hand, the presence of SH3 domains in cytoskeletal proteins like spectrin may facilitate the signal trans- duction from an extracellular signal to the cytoskeleton. The aspects related with microfilaments; mem- brane-microfilament cytoskeletal interactions; Rho, Rac and Cdc 42; and the role of integrins in signal transduction will be analysed in the chapters by Drs Isenberg, Carpenter, Lim and Gutkind. As for microtubules and since these polymers are more abundant in neurons, some of the reviews grouped in this issue deal with the use of neural cells as a model to study the effect of extracellular signals like Apolipoprotein E (article by Dr Pitas), or the interaction of tubulin with cellular receptors (article by Dr Triller), or the microtubule network rearrange- ments upon reception of extracellular signals (article from our group). Also, the role of microtubules on concentrating those enzymes, as kinases needed in signal transduction, will be briefly reviewed in the work of Dr Carpenter, mainly focusing on PI3-kinase. This work could be complemented by that of Dr Inagaki, indicating a possible role of the third component of the cytoskeleton: intermediate fila- ments, in the process of signal transduction. From Centro de Biologia Molecular, “Severo Ochoa”, Facultad de Ciencias, Universidad Autonoma de Madrid, 28049 Madrid, Spain ©1996 Academic Press Ltd seminars in CELL & DEVELOPMENTAL BIOLOGY, Vol 7, 1996: p 681 681
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Transcript of Introduction: Intercellular signals and the cytoskeleton
Introduction: Intercellular signals and the cytoskeletonJesús Avila
THANKS TO THE pioneering studies of Hamburger andLevi-Montalcini (J Exp Zool 111: 457) it is now clearthat some cells require the secreted products fromother cells in order to survive. Indeed Raff andcolleagues (Science 262: 695) have recently suggestedthat probably all mammalian cells, except blasto-meres, need extracellular signals (produced by othercells) for survival. Extracellular signals also make cellsproliferate or differentiate. In the first case, dividingcells undergo replicative senescence after a limitednumber of cell cycles (Campisi, Cell 84: 497). Whenthe cells differentiate, they could adhere to eachother, thus giving rise to the formation of tissues andorgans.
Thus, an increase in the search for survival,proliferation or differentiation factors has occurred inthe last decade (see for example the issue edited by L.Gillespie on Growth Factors in Development in SeminDev Biol, 1991). This study has been mainly comple-mented with the analysis of the receptor moleculespresent in the target cells. The activation of thesereceptors usually results in the modification of certainenzymes like protein kinases involved in signal trans-duction inside the cell (some aspects of this topic havealso been reviewed in Semin Cell Biol).
One of the major consequences of signal transduc-tion is the development of cell morphologicalchanges. The structure responsible for these changesis the cytoskeleton. Thus, it seems very important todetermine the mechanism explaining how an extrac-ellular signal induces cytoskeletal rearrangements.
In the cases of cell–cell interaction, surface proteinsof the two cells could interact with each other andtrigger an intracellular signal that modifies thecytoskeleton, thus determining the morphology of thetissue, as discussed by Gumbiner (Cell 84: 345).
The objective of the present set of reviews is theanalysis of the different steps that take place fromreceiving an extracellular signal to the modification ofthe cytoskeleton. Thus, specific examples of therelationship between signal transduction and the
three elements of the cytoskeleton: microfilaments,intermediate filaments and microtubules are indi-cated. Another purpose of this issue is to discuss thegenerality of these interactions in different cell types.The occurrence of the pathway: extracellular signal →membrane receptors → cytoskeletal rearrangement→ morphological changes, will be a recurrent topicthroughout the present reviews.
In some cases, the reception of an extracellularsignal activates phospholipase C γ that acts onphosphoinositides to which membrane-actin bindingproteins like profilin are bound. This results inchanges in the level of actin polymerization. It is alsoknown that some extracellular signals may activateGTP-binding proteins like Rho, Rac and Cdc 42 whichpromote changes in microfilament organization. Inparticular, Rho protein seems to be involved in thechanges elicited by extracellular matrix componentsthrough their binding to integrins. On the otherhand, the presence of SH3 domains in cytoskeletalproteins like spectrin may facilitate the signal trans-duction from an extracellular signal to thecytoskeleton.
The aspects related with microfilaments; mem-brane-microfilament cytoskeletal interactions; Rho,Rac and Cdc 42; and the role of integrins in signaltransduction will be analysed in the chapters by DrsIsenberg, Carpenter, Lim and Gutkind.
As for microtubules and since these polymers aremore abundant in neurons, some of the reviewsgrouped in this issue deal with the use of neural cellsas a model to study the effect of extracellular signalslike Apolipoprotein E (article by Dr Pitas), or theinteraction of tubulin with cellular receptors (articleby Dr Triller), or the microtubule network rearrange-ments upon reception of extracellular signals (articlefrom our group). Also, the role of microtubules onconcentrating those enzymes, as kinases needed insignal transduction, will be briefly reviewed in thework of Dr Carpenter, mainly focusing on PI3-kinase.This work could be complemented by that of DrInagaki, indicating a possible role of the thirdcomponent of the cytoskeleton: intermediate fila-ments, in the process of signal transduction.From Centro de Biologia Molecular, “Severo Ochoa”, Facultad de
Ciencias, Universidad Autonoma de Madrid, 28049 Madrid,Spain
©1996 Academic Press Ltd
seminars in CELL & DEVELOPMENTAL BIOLOGY, Vol 7, 1996: p 681
681
