Wnts and TGFβ in synaptogenesis: old friends signalling at new places

Abstract

The formation of mature synaptic connections involves the targeted transport and aggregation of synaptic vesicles, the gathering of presynaptic release sites and the clustering of postsynaptic neurotransmitter receptors and ion channels. Positional cues are required to orient the cytoskeleton in the direction of neuronal outgrowth, and also to direct the juxtaposition of synaptic protein complexes at the pre-and postsynaptic membranes. Both anterograde and retrograde factors are thought to contribute positional information during synaptic differentiation, and recent studies in vertebrates and invertebrates have begun to uncover a new role in this process for proteins that are essential for pattern formation in the early embryo.Cells use distinct mechanisms for transmitting information to their neighbours, depending on their tissue type and environment. This intercellular communication is vital during the early stages of development, when nascent cells acquire their identities to organize the body plan, and later as mature cells work together to maintain function and lifestyle. Not surprisingly, disruption of intercellular communication leads to various diseases, ranging from cancer to mental retardation, so understanding the fundamental nature of cell-talk remains one of the most important areas of biology.In the nervous system, the elemental means of communication between cells is synaptic transmission. Chemical synapses are asymmetrical cellular junctions that are involved in the directional transmission of electrical signals. Essential to the high speed and efficiency at which neurons communicate is the exquisite molecular organization of the pre-and postsynaptic apparatus. In the presynaptic compartment, neurotransmitter-laden vesicles are poised at ACTIVE ZONES, ready for immediate release, and the calcium channels that are required to trigger exocytosis are spatially linked to the secretory machinery. At the postsynaptic membrane, neurotransmitter receptors form high-density clusters that are directly apposed to the active zones. The proper development and functioning of synaptic Correspondence to V.B. vbudnik@ bio.umass.edu. DATABASES The following terms in this article are linked online to: Entrez: http://www.ncbi.nlm.nih.gov/Entrez/Tbl1 FlyBase: http://flybase.bio.indiana.edu/ Arm | Arr Once synapses are formed, the strengthening and weakening of synaptic connections is believed to be central to the processes of learning and memory, and also to the regeneration of synaptic connectivity after a traumatic injury. This synaptic plasticity also depends on communication between pre-and postsynaptic compartments 1 , and it includes both anterograde and retrograde signals. The existence of a retrograde signal has been postulated to account for the adjustment of presynaptic outputs that result from changes in postsynaptic responses. For example, at the fly neuromuscular junction (NMJ), decreased muscle responses to neuronal stimuli can be brought about by manipulation of glutamate receptor (GluR) levels...

The atypical cadherin flamingo regulates synaptogenesis and helps prevent axonal and synaptic degeneration in Drosophila

“…Other molecules are more directly involved in synaptogenesis, synaptic growth, or maintenance. These molecules include bone morphogenetic protein (Alberle et al, 2002;Marques et al, 2002;Rawson et al, 2003;McCabe et al, 2003;Keshishian and Kim, 2004), ubiquitin (Oh et al, 1994;DiAntonio et al, 2001;Murphey and Godenschwege, 2002;DiAntonio and Hicke, 2004), cell adhesion molecules (Washbourne et al, 2004), and Wingless signaling components (Packard et al, 2003;Charron and Tessier-Lavigne, 2005).…”

New roles for astrocytes: Regulation of CNS synaptogenesis

“…This new triad of actors has prompted the concept of the 'tripartite synapse', which states that 'synaptically associated astrocytes should be viewed as integral modulatory elements of synapses ' [6]. However, recent reviews on the development of synapses [7][8][9][10][11][12][13] reveal that this fundamental process is still considered an entirely neuronal event. This article summarizes evidence that this view could be outdated and that astrocytes might take part in this process as well.…”

HtrA1-dependent proteolysis of TGF-β controls both neuronal maturation and developmental survival

“…Transforming growth factor-b controls a plethora of neuronal and glial functions throughout life, under normal or pathological conditions including the functional neuronal connectivity, 1 apoptotic pathways, 2,3 glutamatergic signalling 4 and amyloidb turnover. 5 TGF-b isoforms elicit their cell type-specific responses through the ligand-induced formation of a heteromeric receptor complex between the serine/threonine kinases TbR-I and TbR-II: the type II receptor binds TGF-b by its own, then recruits the type I receptor, allowing the transphosphorylation-mediated activation of TbR-I.…”

“…However, an ever increasing complexity in the canonical TGF-b intracellular cascade emerges, with the discovery of cross-talks with other signalling pathways such as mitogen-activated protein kinases or Wnt and the description of multiple regulatory factors, including Ski and SnoN or processes such as ubiquitination. 1,7 The bacterial serine-protease HtrA, also known as DegP, is a heat shock-induced envelope-associated serine protease. 8 Its main role is to recognize and degrade misfolded proteins in the periplasm, combining a dual activity of chaperone and protease.…”