Abstract:
:Changes in the actin cytoskeleton are a primary mechanism mediating the morphological and functional plasticity that underlies learning and memory. The synaptic Ras homologous (Rho) guanine nucleotide exchange factors (GEFs) Kalirin and Trio have emerged as central regulators of actin dynamics at the synapse. The increased attention surrounding Kalirin and Trio stems from the growing evidence for their roles in the etiology of a wide range of neurodevelopmental and neurodegenerative disorders. In this Review, we discuss recent findings revealing the unique and diverse functions of these paralog proteins in neurodevelopment, excitatory synaptic transmission, and plasticity. We additionally survey the growing literature implicating these proteins in various neurological disorders.
journal_name
Trends Neuroscijournal_title
Trends in neurosciencesauthors
Paskus JD,Herring BE,Roche KWdoi
10.1016/j.tins.2020.05.002subject
Has Abstractpub_date
2020-07-01 00:00:00pages
505-518issue
7eissn
0166-2236issn
1878-108Xpii
S0166-2236(20)30104-1journal_volume
43pub_type
杂志文章,评审abstract::Rather than merely a nuisance, noise in biological systems is a useful property. Before patch-clamp methods were invented, analysis of membrane current noise provided the first solid, if indirect, evidence for the existence of ion-conducting pores with discrete conductance levels. Although supplanted by single-channel...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/s0166-2236(98)01238-7
更新日期:1998-04-01 00:00:00
abstract::Activation of the complement system has been reported in a variety of inflammatory diseases and neurodegenerative processes of the CNS. Recent evidence indicates that complement proteins and receptors are synthesized on or by glial cells and, surprisingly, neurons. Among these proteins are the receptors for the chemot...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/s0166-2236(98)01390-3
更新日期:1999-09-01 00:00:00
abstract::In monkeys, the rostral part of ventral premotor cortex (area F5) contains neurons that discharge, both when the monkey grasps or manipulates objects and when it observes the experimenter making similar actions. These neurons (mirror neurons) appear to represent a system that matches observed events to similar, intern...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/s0166-2236(98)01260-0
更新日期:1998-05-01 00:00:00
abstract::Acute inflammation plays an important role in host tissue defense against injury and infection, and also subsequent tissue repair. In the central nervous system parenchyma, following many types of insults, the acute inflammatory response to rapid neuronal degeneration or challenge with inflammatory substances differs ...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/0166-2236(93)90180-t
更新日期:1993-07-01 00:00:00
abstract::Imagine the decisions you might make while playing a simple game like 'matching pennies'. At each play, you and your opponent, say the mathematician John vonNeumann, each lay down a penny heads or tails up. If both pennies show the same side, vonNeumann wins, if not, you win. Before each play, you have the subjective ...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/s0166-2236(00)01932-9
更新日期:2001-11-01 00:00:00
abstract::Priming is the process by which vesicles become available for fusion at nerve terminals and is modulated by numerous proteins and second messengers. One of the prominent members of this diverse family is tomosyn. Tomosyn has been identified as a syntaxin-binding protein; it inhibits vesicle priming, but its mode of ac...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2009.01.004
更新日期:2009-05-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a lethal disease that is characterized by the relentless death of motoneurons. Mutations to Cu-Zn superoxide dismutase (SOD), though occurring in just 2-3% of individuals with ALS, remain the only proven cause of the disease. These mutations structurally weaken SOD, which indirec...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/s0166-2236(00)01981-0
更新日期:2001-11-01 00:00:00
abstract::Glial fibrillary acidic protein (GFAP) is an intermediate filament (IF) III protein uniquely found in astrocytes in the central nervous system (CNS), non-myelinating Schwann cells in the peripheral nervous system (PNS), and enteric glial cells. GFAP mRNA expression is regulated by several nuclear-receptor hormones, gr...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2015.04.003
更新日期:2015-06-01 00:00:00
abstract::Integrins comprise a large family of heterodimeric proteins that mediate cell-cell and cell-extracellular-matrix adhesive connections. There is an extensive literature on their importance in neural development and cancer, but evidence for the existence of integrins in the adult CNS has emerged only recently. With grow...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/0166-2236(96)89623-8
更新日期:1996-02-01 00:00:00
abstract::The production by the pyridine MPTP of a parkinsonian syndrome strikingly similar to the 'idiopathic' disorder, and the paucity of evidence supporting a hereditary or infectious etiology for Parkinson's disease (PD), have stimulated a search for environmental chemicals resembling MPTP that might cause PD. In support o...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/0166-2236(89)90135-5
更新日期:1989-02-01 00:00:00
abstract::Maladaptive responses to stress and the associated hypersecretion of glucocorticoids cause psychopathologies ranging from hyperemotional states and mood dysfunction to cognitive impairments. Research in both humans and animal models has begun to identify morphological correlates of these functional changes. These incl...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2012.08.006
更新日期:2012-12-01 00:00:00
abstract::Among the many calcium-binding proteins in the nervous system, parvalbumin, calbindin-D28K and calretinin are particularly striking in their abundance and in the specificity of their distribution. They can be found in different subsets of neurons in many brain regions. Although it is not yet known whether they play a ...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/0166-2236(92)90081-i
更新日期:1992-08-01 00:00:00
abstract::Rett syndrome is a neurodevelopmental disorder that primarily affects females and is caused by mutations in the methyl-CpG-binding-protein 2 (MECP2) gene. Initially, MeCP2 had been shown to be a repressor of gene transcription. In their 2008 paper, Chahrour and colleagues (DOI: 10.1126/science.1153252) reported that M...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2017.11.005
更新日期:2018-02-01 00:00:00
abstract::A growing body of work is investigating the safety and efficacy of light in Parkinson's disease (PD). Here we discuss the potential of this emerging therapy to improve both motor and non-motor symptoms of PD. We also highlight directions for future basic, translational, and clinical research that are critical for the ...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2018.03.002
更新日期:2018-05-01 00:00:00
abstract::The proportional relation between circulating vasopressin concentration and plasma osmolality is fundamental for body fluid homeostasis. Although changes in the sensitivity of this relation are associated with pathophysiological conditions, central mechanisms modulating osmoregulatory gain are unknown. Here, we review...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2009.11.004
更新日期:2010-02-01 00:00:00
abstract::The term neuropeptide was advanced by de Wied and collaborators in the early seventies. At that time, they defined neuropeptides as endogenous substances synthesized in nerve cells and involved in nervous system functions. Since then, several studies have revealed that the very same 'neuropeptides' are also expressed ...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2003.09.003
更新日期:2003-11-01 00:00:00
abstract::The ability of neurons to modulate the strength of their synaptic connections has been shown to depend on the relative timing of pre- and postsynaptic action potentials. This form of synaptic plasticity, called spike-timing-dependent plasticity (STDP), has become an attractive model for learning at the single-cell lev...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2007.06.010
更新日期:2007-09-01 00:00:00
abstract::The molecular nature of the metabotropic GABA(B) receptor was for some time a mystery, however it was recently discovered that two related G-protein-coupled receptors have to heterodimerize to form the functional GABA(B) receptor at the cell surface. This review discusses the most recent findings in the rapidly expand...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/s0166-2236(00)01815-4
更新日期:2001-05-01 00:00:00
abstract::To successfully interact with their environments, developing organisms need to correctly process sensory information and generate motor outputs appropriate to their size and structure. Patterned sensory experience has long been known to induce various forms of developmental plasticity that ultimately shape mature neur...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2010.01.003
更新日期:2010-04-01 00:00:00
abstract::Recently, two large multigene families of putative G-protein-linked receptors that are expressed in distinct subpopulations of neurones in the vomeronasal organ have been identified. These receptors probably mediate pheromone detection. The most surprising aspects of these findings are that there are so many receptors...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/s0166-2236(98)01274-0
更新日期:1998-11-01 00:00:00
abstract::As a neurodevelopmental disorder with serious lifelong consequences, autism has received considerable attention from neuroscientists and geneticists. We present a hypothesis of mechanisms plausibly affected during brain development in autism, based on neural pathways that are associated with social behavior and connec...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2019.05.002
更新日期:2019-07-01 00:00:00
abstract::Recent opinion surveys suggest that the majority of the public is willing to accept the use of animals in research if high standards of welfare and effective regulation are in place. The public appears unaware that such standards have existed for some time. The scientific community should now re-focus its communicatio...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/s0166-2236(00)02035-x
更新日期:2002-03-01 00:00:00
abstract::Release probability (P) appears to be a major factor that influences the pattern of transmitter release. At cortical pyramidal axon inputs onto different classes of target cells, very different release patterns are observed, patterns that correlate with release probability. Simplistically, 'low P' synapses display fac...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/s0166-2236(00)01580-0
更新日期:2000-07-01 00:00:00
abstract::Multiple sclerosis (MS), an incurable but manageable disorder, is characterized by chronic inflammatory demyelination and neurodegeneration in the central nervous system. Although the primary cause of this often devastating disease remains elusive, major therapeutic advances have occurred during the past two decades. ...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2009.12.002
更新日期:2010-03-01 00:00:00
abstract::There are pluripotent stem cells in the adult brain that might not be very different from those found in bone marrow. Recent and profound advances in the field of neuropoiesis, which often rely on insights from studies of hematopoiesis and in some instances use cross-paradigms with this field, have already revealed th...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/s0166-2236(99)01416-2
更新日期:1999-08-01 00:00:00
abstract::Compromise of the ubiquitin-proteasome system (UPS) is a potential basis for multiple physiological abnormalities and pathologies in the CNS. This could be because reduced protein turnover leads to bulk intracellular protein accumulation. However, conditions associated with compromised UPS function are also associated...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2006.11.003
更新日期:2007-01-01 00:00:00
abstract::Aging is the most important risk factor for common neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. Aging in the central nervous system has been associated with elevated mutation load in mitochondrial DNA, defects in mitochondrial respiration and increased oxidative damage. These observations ...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2008.02.008
更新日期:2008-05-01 00:00:00
abstract::Huntington's disease (HD) is an autosomal, dominantly inherited neurodegenerative disorder that is characterized by abnormal involuntary movements (chorea), intellectual impairment and selective neuronal loss. The expansion of a polymorphic trinucleotide repeat (the sequence CAG that codes for glutamine) to a length t...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/s0166-2236(99)01415-0
更新日期:1999-06-01 00:00:00
abstract::The brain includes multiple types of interconnected excitatory and inhibitory neurons that together allow us to move, think, feel, and interact with the environment. Inhibitory interneurons (INs) comprise a small, heterogeneous fraction, but they exert a powerful and tight control over neuronal activity and consequent...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2017.05.004
更新日期:2017-07-01 00:00:00
abstract::Recognition of foreign or misplaced nucleic acids is one of the principal modes by which the immune system detects pathogenic entities. When cytosolic DNA is sensed, a signal is relayed via the cGAS-STING pathway: this involves the activation of cyclic GMP-AMP (cGMP-AMP) synthase (cGAS) and generation of the cyclic di...
journal_title:Trends in neurosciences
pub_type: 杂志文章,评审
doi:10.1016/j.tins.2020.10.008
更新日期:2021-02-01 00:00:00