How integrin phosphorylations regulate cell adhesion and signaling

Cell adhesion is essential for the formation of organs, cellular migration, and interaction with target cells and the extracellular matrix. Integrins are large protein alpha/13-chain heterodimers and form a major family of cell adhesion molecules. Recent research has dramatically increased our knowledge of how integrin phos-phorylations regulate integrin activity. Phosphorylations determine the signaling complexes formed on the cytoplasmic tails, regulating downstream signaling. alpha-Chain phosphorylation is necessary for inducing 13-chain phosphorylation in LFA-1, and the crosstalk from one integrin to another activating or inactivating its function is in part mediated by phosphorylation of 13-chains. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus receptor angiotensin-converting enzyme 2 (ACE2) and possible integrin coreceptors may crosstalk and induce a phosphorylation switch and autophagy.Peer reviewe

Ihmisen perimän selvittäminen vasta alkua

Ihmisen perimän selvittäminen on epäilemättä tämän päivän tieteen tärkein projekti, ainakin kun elämästä on kysymys. The "Human Genome Project" aloitettiin vuonna 1986 ja jo vuonna 1987 saatiin aikaan ensimmäinen hyvin yksinkertainen geenikartta, joka käsitteli 400 ihmisen geenimerkkiä. 1990 muodostettiin kansainvälinen järjestö, jonka rahoittamiseen käytettiin monen maan julkisia tutkimusvaroja. Sen tehtäväksi tuli selvittää ihmisen koko perimä. Projekti on edennyt ennakoitua nopeammin ja kesäkuun 26. päivänä 2000 saatiin valmiiksi ensimmäinen karkea koko genomia käsittävä sekvensointityö. Tästä saavutuksesta ilmoitettiin samaan aikaan Valkoisesta talosta ja Downing Street 10:stä. Euroopan kontribuutio oli noin kolmannes ja koordinoitiin Cambridgestä

Vuoden Tiedekirja 1997-palkinto Suomen luonnon sata vuotta -teokselle

Vuoden Tiedekirja 1997 -palkinto on myönnetty toimittaja Juhani Mänttärille ja Suomen Biologian Seura Vanamolle teoksesta Suomen luonnon sata vuotta. Palkinto on suuruudeltaan yhteensä 20 000 mk. Pääpalkinnon lisäksi myönnettiin kolmelle teokselle kunniamaininnat. Palkinnot jaettiin Helsingissä Tieteiden talolla Tieteellisten seurain valtuuskunnan vuosikokouksen yhteydessä 27. maaliskuuta. Palkinnon myöntävät yhdessä Tieteellisten seurain valtuuskunta ja Suomen tiedekustantajien liitto

Regulation of Dynamic Cell Adhesion by Integrin-Integrin Crosstalk

Most cells express several integrins. The integrins are able to respond to various cellular functions and needs by modifying their own activation state, but in addition by their ability to regulate each other by activation or inhibition. This crosstalk or transdominant regulation is strictly controlled. The mechanisms resulting in integrin crosstalk are incompletely understood, but they often involve intracellular signalling routes also used by other cell surface receptors. Several studies show that the integrin cytoplasmic tails bind to a number of cytoskeletal and adaptor molecules in a regulated manner. Recent work has shown that phosphorylations of integrins and key intracellular molecules are of pivotal importance in integrin-cytoplasmic interactions, and these in turn affect integrin activity and crosstalk. The integrin β-chains play a central role in regulating crosstalk. In addition to Integrin-integrin crosstalk, crosstalk may also occur between integrins and related receptors, including other adhesion receptors, growth factor and SARS-CoV-2 receptors

MiSuomen Tiedeseura täyttää 160 vuotta

Suomen Tiedeseura (Finska Vetenskaps-Societeten) on Suomen vanhin tiedeakatemia. Kun se perustettiin vuonna 1838, Suomessa oli jo muutama tieteellinen yhdistys olemassa: Societas pro Fauna et Flora Fennica (1821), Suomalaisen Kirjallisuuden Seura (1831) ja Finska Läkaresällskapet (1835). Suomen Tiedeseuran sisarakatemia, Suomalainen Tiedeakatemia, perustettiin 1908. Tiedeakatemiat eroavat oleellisesti tieteellisistä yhdistyksistä siinä, että niihin ei liitytä, vaan perusteellisen evaluaation ja karsinnan perusteella akatemiat valitsevat uudet jäsenensä,joiden määrä on rajoitettu. Lisäksi ne eivät voi periä jäsenmaksuja

Regulation of Dynamic Cell Adhesion by Integrin-Integrin Crosstalk

Most cells express several integrins. The integrins are able to respond to various cellular functions and needs by modifying their own activation state, but in addition by their ability to regulate each other by activation or inhibition. This crosstalk or transdominant regulation is strictly controlled. The mechanisms resulting in integrin crosstalk are incompletely understood, but they often involve intracellular signalling routes also used by other cell surface receptors. Several studies show that the integrin cytoplasmic tails bind to a number of cytoskeletal and adaptor molecules in a regulated manner. Recent work has shown that phosphorylations of integrins and key intracellular molecules are of pivotal importance in integrin-cytoplasmic interactions, and these in turn affect integrin activity and crosstalk. The integrin β-chains play a central role in regulating crosstalk. In addition to Integrin-integrin crosstalk, crosstalk may also occur between integrins and related receptors, including other adhesion receptors, growth factor and SARS-CoV-2 receptors

ICAM-5 affects spine maturation by regulation of NMDA receptor binding to alpha-actinin

ICAM-5 is a negative regulator of dendritic spine maturation and facilitates the formation of filopodia. Its absence results in improved memory functions, but the mechanisms have remained poorly understood. Activation of NMDA receptors induces ICAM-5 ectodomain cleavage through a matrix metalloproteinase (MMP)-dependent pathway, which promotes spine maturation and synapse formation. Here, we report a novel, ICAM-5-dependent mechanism underlying spine maturation by regulating the dynamics and synaptic distribution of a-actinin. We found that GluN1 and ICAM-5 partially compete for the binding to alpha-actinin; deletion of the cytoplasmic tail of ICAM-5 or ablation of the gene resulted in increased association of GluN1 with alpha-actinin, whereas internalization of ICAM-5 peptide perturbed the GluN1/alpha-actinin interaction. NMDA treatment decreased alpha-actinin binding to ICAM-5, and increased the binding to GluN1. Proper synaptic distribution of alpha-actinin requires the ICAM-5 cytoplasmic domain, without which alpha-actinin tended to accumulate in filopodia, leading to F-actin reorganization. The results indicate that ICAM-5 retards spine maturation by preventing reorganization of the actin cytoskeleton, but NMDA receptor activation is sufficient to relieve the brake and promote the maturation of spines.Peer reviewe

Phosphorylation of the α-chain in the integrin LFA-1 enables β2-chain phosphorylation and α-actinin binding required for cell adhesion

The integrin leukocyte function-associated antigen-1 (LFA-1) plays a pivotal role in leukocyte adhesion and migration, but the mechanism(s) by which this integrin is regulated has remained incompletely understood. LFA-1 integrin activity requires phosphorylation of its 2-chain and interactions of its cytoplasmic tail with various cellular proteins. The -chain is constitutively phosphorylated and necessary for cellular adhesion, but how the -chain regulates adhesion has remained enigmatic. We now show that substitution of the -chain phosphorylation site (S1140A) in T cells inhibits the phosphorylation of the functionally important Thr-758 in the 2-chain, binding of -actinin and 14-3-3 protein, and expression of an integrin-activating epitope after treatment with the stromal cell-derived factor-1. The presence of this substitution resulted in a loss of cell adhesion and directional cell migration. Moreover, LFA-1 activation through the T-cell receptor in cells expressing the S1140A LFA-1 variant resulted in less Thr-758 phosphorylation, -actinin and talin binding, and cell adhesion. The finding that the LFA-1 -chain regulates adhesion through the -chain via specific phosphorylation at Ser-1140 in the -chain has not been previously reported and emphasizes that both chains are involved in the regulation of LFA-1 integrin activity.Peer reviewe