Presynaptic LRP4 Promotes Synapse Number and Function of Excitatory CNS Neurons

SUMMARYPrecise coordination of synaptic connections ensures proper information flow within circuits. The activity of presynaptic organizing molecules signaling to downstream pathways is essential for such coordination, though such entities remain incompletely known. We show that LRP4, a conserved transmembrane protein known for its postsynaptic roles, functions presynaptically as an organizing molecule. In the Drosophila brain, LRP4 preferentially localizes to excitatory neuron terminals at or near active zones. Loss of presynaptic LRP4 reduces excitatory (not inhibitory) synapse number, impairs active zone architecture, and abolishes olfactory attraction - the latter of which can be suppressed by reducing presynaptic GABAB receptors. LRP4 overexpression increases synapse number in excitatory and inhibitory neurons, suggesting an instructive role and a common downstream synapse addition pathway. Mechanistically, LRP4 functions via the conserved kinase SRPK79D to ensure normal synapse number and behavior. This highlights a presynaptic function for LRP4, enabling deeper understanding of how synapse organization is coordinated.

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Presynaptic LRP4 promotes synapse number and function of excitatory CNS neurons

eLife ◽

10.7554/elife.27347 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 26

Author(s):

Timothy J Mosca ◽

David J Luginbuhl ◽

Irving E Wang ◽

Liqun Luo

Keyword(s):

Transmembrane Protein ◽

Gabab Receptors ◽

Inhibitory Neurons ◽

Synaptic Connections ◽

Presynaptic Function ◽

Drosophila Brain ◽

Active Zones ◽

And Function ◽

And Behavior ◽

Addition Pathway

Precise coordination of synaptic connections ensures proper information flow within circuits. The activity of presynaptic organizing molecules signaling to downstream pathways is essential for such coordination, though such entities remain incompletely known. We show that LRP4, a conserved transmembrane protein known for its postsynaptic roles, functions presynaptically as an organizing molecule. In the Drosophila brain, LRP4 localizes to the nerve terminals at or near active zones. Loss of presynaptic LRP4 reduces excitatory (not inhibitory) synapse number, impairs active zone architecture, and abolishes olfactory attraction - the latter of which can be suppressed by reducing presynaptic GABAB receptors. LRP4 overexpression increases synapse number in excitatory and inhibitory neurons, suggesting an instructive role and a common downstream synapse addition pathway. Mechanistically, LRP4 functions via the conserved kinase SRPK79D to ensure normal synapse number and behavior. This highlights a presynaptic function for LRP4, enabling deeper understanding of how synapse organization is coordinated.

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Selective Postnatal Excitation of Neocortical Pyramidal Neurons Results in Distinctive Behavioral and Circuit Deficits in Adulthood

10.1101/2020.01.18.911347 ◽

2020 ◽

Cited By ~ 1

Author(s):

William E. Medendorp ◽

Akash Pal ◽

Madison Waddell ◽

Andreas Björefeldt ◽

Christopher I. Moore ◽

...

Keyword(s):

Experimental Approach ◽

Pyramidal Neurons ◽

Autism Spectrum ◽

Inhibitory Neurons ◽

Neocortical Neurons ◽

And Function ◽

Circuit Function ◽

And Behavior ◽

The Impact

SummaryIn leading models of Autism Spectrum Disorder, and in human data, the efficacy of outgoing cortical connectivity transitions from overly exuberant to languid from early development to adulthood. This transition begs the question of whether the early enhancement in excitation might be a common driver, across etiologies, of these symptoms. We directly tested this concept by chemogenetically driving neuronal activity in neocortical neurons during postnatal days 4-14. Hyperexcitation of Emx1-, but not dopamine transporter-, parvalbumin-, or Dlx5/6-expressing neurons led to decreased social interaction and increased grooming activity in adult animals. In vivo optogenetic interrogation in adults revealed decreased baseline but increased stimulus-evoked firing rates of pyramidal neurons, impaired recruitment of inhibitory neurons and reduced cortico-striatal communication. These results directly support the prediction that changed firing in developing circuits irreversibly alters adult circuit function that leads to maladaptive changes in behaviors. This experimental approach offers a valuable platform to study the impact of disruption of developmental neural activity on the formation and function of adult neural circuits and behavior.

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Structure and function of neural networks in the retina

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100102213 ◽

1988 ◽

Vol 46 ◽

pp. 26-27

Author(s):

Peter Sterling

Keyword(s):

Ganglion Cells ◽

Three Dimensional ◽

Structure And Function ◽

Synaptic Connections ◽

Visual Axis ◽

One Dimensional ◽

Cat Retina ◽

Ultrathin Sections ◽

And Function ◽

Insight Into

The synaptic connections in cat retina that link photoreceptors to ganglion cells have been analyzed quantitatively. Our approach has been to prepare serial, ultrathin sections and photograph en montage at low magnification (˜2000X) in the electron microscope. Six series, 100-300 sections long, have been prepared over the last decade. They derive from different cats but always from the same region of retina, about one degree from the center of the visual axis. The material has been analyzed by reconstructing adjacent neurons in each array and then identifying systematically the synaptic connections between arrays. Most reconstructions were done manually by tracing the outlines of processes in successive sections onto acetate sheets aligned on a cartoonist's jig. The tracings were then digitized, stacked by computer, and printed with the hidden lines removed. The results have provided rather than the usual one-dimensional account of pathways, a three-dimensional account of circuits. From this has emerged insight into the functional architecture.

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SISTEM PENDUKUNG KEPUTUSAN ANALISIS KEPUASAN MAHASISWA TERHADAP PENGGUNAAN SARANA LABORATORIUM SISTEM INFORMASI

Jurnal Sains dan Informatika ◽

10.22216/jsi.v4i2.3735 ◽

2018 ◽

Vol 4 (2) ◽

pp. 150

Author(s):

Rahmadini Darwas

Keyword(s):

Service Quality ◽

Learning Process ◽

Quality Of Services ◽

Laboratory Facilities ◽

Cold Room ◽

And Function ◽

And Behavior ◽

Attitudes And Behavior ◽

Role And Function

Abstract Laboratory is one of the supporting facilities in im[roving the learning process. Problems found by students regarding the information system laboratory facilities at STMIK Indonesia Padang are the computers that suddenly die when operated, the less cold room, display data is blurred, making the inconvenience in the learning process that causes the students less satisfied with the services provided. Students will feel satisfied if the service is expected to match the received. Therefore, a decision support system is needed to analyze the quality of services provided to the students so that it can support the role and function of the laboratory optimally and what attributes need to be improved the quality of service. The method used is Fuzzy Service Quality (Servqual) method. The results showed that the service quality received was not in accordance with the expected because there is a gap of -1.55 for tangibles dimension. Attributes that need to be improved the quality of services are laboratory space is cool and comfortable, the use of laboratories relevant to the field of science, the responsibility of laboratory assistant, the availability of professional teachers and attitudes and behavior of labor officers. Abstrak Laboratorium merupakan salah satu fasilitas pendukung dalam meningkatkan proses pembelajaran. Permasalahan yang ditemukan mahasiswa mengenai fasilitas laboratorium sistem informasi pada STMIK Indonesia Padang adalah komputer yang tiba-tiba mati saat dioperasikan, ruangan yang kurang dingin, data display yang buram sehingga membuat ketidaknyamanan dalam proses pembelajaran yang menyebabkan mahasiswa kurang puas terhadap layanan yang diberikan. Mahasiswa akan merasa puas apabila layanan yang diharapkan sesuai dengan yang diterima. Oleh sebab itu, diperlukan suatu sistem pendukung keputusan untuk menganalisis kualitas layanan yang diberikan kepada mahasiswa sehingga dapat mendukung peran dan fungsi laboratorium secara optimal serta atribut apa saja yang perlu ditingkatkan kualitas layanannya. Metode yang digunakan adalah metode Fuzzy Service Quality (Servqual). Hasil penelitian menunjukkan bahwa kualitas layanan yang diterima belum sesuai dengan yang diharapkan karena terdapat gap sebesar -1.55 untuk dimensi tangibles. Atribut yang perlu ditingkatkan kualitas layanannya yaitu ruangan laboratorium yang sejuk dan nyaman, penggunaan laboratorium yang relevan dengan bidang ilmu, tanggungjawab asisten labor, tersedianya tenaga pengajar yang professional dan sikap serta perilaku petugas laborKata kunci : sistem pendukung keputusan, laboratorium, fuzzy, servqual

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Understanding Motivating Operations and the Impact on the Function of Behavior

Intervention in School and Clinic ◽

10.1177/1053451220914901 ◽

2020 ◽

Vol 56 (2) ◽

pp. 119-122

Author(s):

Doris Adams Hill ◽

Theoni Mantzoros ◽

Jonté C. Taylor

Keyword(s):

Behavioral Interventions ◽

Special Educators ◽

Motivating Operations ◽

Behavior Intervention Plans ◽

Education Professionals ◽

Functional Behavior ◽

Special Education Professionals ◽

And Function ◽

And Behavior ◽

The Impact

Special educators are often considered the experts in their school when it comes to developing functional behavior assessments (FBA) and behavior intervention plans (BIP), yet rarely are they trained much beyond basic antecedents, behaviors, and consequences (ABC). This column discusses concepts that will expand special education professionals’ knowledge to make better decisions regarding interventions for the students they serve. Specifically, the focus is on motivating operations (MO) and function-based interventions and the implications of these on behavior. Knowledge of the concept of MOs can enhance a teacher’s ability to provide evidence-based interventions and more fully developed behavioral interventions for students in their purview.

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Prediction of Functional Consequences of Missense Mutations in ANO4 Gene

International Journal of Molecular Sciences ◽

10.3390/ijms22052732 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2732

Author(s):

Nadine Reichhart ◽

Vladimir M. Milenkovic ◽

Christian H. Wetzel ◽

Olaf Strauß

Keyword(s):

Transmembrane Protein ◽

Functional Characterization ◽

Missense Mutations ◽

Mutant Proteins ◽

Functional Consequences ◽

New Perspective ◽

The Stability ◽

Dynamics Simulations ◽

And Function

The anoctamin (TMEM16) family of transmembrane protein consists of ten members in vertebrates, which act as Ca2+-dependent ion channels and/or Ca2+-dependent scramblases. ANO4 which is primarily expressed in the CNS and certain endocrine glands, has been associated with various neuronal disorders. Therefore, we focused our study on prioritizing missense mutations that are assumed to alter the structure and stability of ANO4 protein. We employed a wide array of evolution and structure based in silico prediction methods to identify potentially deleterious missense mutations in the ANO4 gene. Identified pathogenic mutations were then mapped to the modeled human ANO4 structure and the effects of missense mutations were studied on the atomic level using molecular dynamics simulations. Our data show that the G80A and A500T mutations significantly alter the stability of the mutant proteins, thus providing new perspective on the role of missense mutations in ANO4 gene. Results obtained in this study may help to identify disease associated mutations which affect ANO4 protein structure and function and might facilitate future functional characterization of ANO4.

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Bruchpilot, a Protein with Homology to ELKS/CAST, Is Required for Structural Integrity and Function of Synaptic Active Zones in Drosophila

Neuron ◽

10.1016/j.neuron.2006.06.022 ◽

2006 ◽

Vol 51 (2) ◽

pp. 275 ◽

Cited By ~ 6

Author(s):

Dhananjay A. Wagh ◽

Tobias M. Rasse ◽

Esther Asan ◽

Alois Hofbauer ◽

Isabell Schwenkert ◽

...

Keyword(s):

Structural Integrity ◽

Active Zones ◽

And Function

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Regulation of M3 Muscarinic Receptor Expression and Function by Transmembrane Protein 147

Molecular Pharmacology ◽

10.1124/mol.110.067363 ◽

2010 ◽

Vol 79 (2) ◽

pp. 251-261 ◽

Cited By ~ 16

Author(s):

Erica Rosemond ◽

Mario Rossi ◽

Sara M. McMillin ◽

Marco Scarselli ◽

Julie G. Donaldson ◽

...

Keyword(s):

Muscarinic Receptor ◽

Transmembrane Protein ◽

Receptor Expression ◽

And Function ◽

M3 Muscarinic Receptor

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The Role of the CX3CL1-CX3CR1 Axis in Renal Disease

AJP Renal Physiology ◽

10.1152/ajprenal.00059.2021 ◽

2021 ◽

Author(s):

Diana Hamdan ◽

Lisa A. Robinson

Keyword(s):

Therapeutic Potential ◽

Kidney Diseases ◽

Transmembrane Protein ◽

Soluble Form ◽

Protective Effects ◽

Chronic Kidney Diseases ◽

The Family ◽

Soluble Species ◽

And Function

Excessive infiltration of immune cells into the kidney is a key feature of acute and chronic kidney diseases. The family of chemokines are key drivers of this process. CX3CL1 (fractalkine) is one of two unique chemokines synthesized as a transmembrane protein which undergoes proteolytic cleavage to generate a soluble species. Through interacting with its cognate receptor, CX3CR1, CX3CL1 was originally shown to act as a conventional chemoattractant in the soluble form, and as an adhesion molecule in the transmembrane form. Since then, other functions of CX3CL1 beyond leukocyte recruitment have been described, including cell survival, immunosurveillance, and cell-mediated cytotoxicity. This review summarizes diverse roles of CX3CL1 in kidney disease and potential uses as a therapeutic target and novel biomarker. As the CX3CL1-CX3CR1 axis has been shown to contribute to both detrimental and protective effects in various kidney diseases, a thorough understanding of how the expression and function of CX3CL1 are regulated is needed to unlock its therapeutic potential.

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PIN-FORMED 1 regulates cell fate at the periphery of the shoot apical meristem

Development ◽

10.1242/dev.127.23.5157 ◽

2000 ◽

Vol 127 (23) ◽

pp. 5157-5165 ◽

Cited By ~ 13

Author(s):

T. Vernoux ◽

J. Kronenberger ◽

O. Grandjean ◽

P. Laufs ◽

J. Traas

Keyword(s):

Cell Fate ◽

Apical Meristem ◽

Transmembrane Protein ◽

Loss Of Function ◽

Hybrid Identity ◽

Hormone Transport ◽

Early Markers ◽

Ideal Tool ◽

And Function

The process of organ positioning has been addressed, using the pin-formed 1 (pin1) mutant as a tool. PIN1 is a transmembrane protein involved in auxin transport in Arabidopsis. Loss of function severely affects organ initiation, and pin1 mutants are characterised by an inflorescence meristem that does not initiate any flowers, resulting in the formation of a naked inflorescence stem. This phenotype, combined with the proposed role of PIN1 in hormone transport, makes the mutant an ideal tool to study organ formation and phyllotaxis, and here we present a detailed analysis of the molecular modifications at the shoot apex caused by the mutation. We show that meristem structure and function are not severely affected in the mutant. Major alterations, however, are observed at the periphery of the pin1 meristem, where organ initiation should occur. Although two very early markers of organ initiation, LEAFY and AINTEGUMENTA, are expressed at the periphery of the mutant meristem, the cells are not recruited into distinct primordia. Instead a ring-like domain expressing those primordium specific genes is observed around the meristem. This ring-like domain also expresses a boundary marker, CUP-SHAPED COTYLEDON 2, involved in organ separation, showing that the zone at the meristem periphery has a hybrid identity. This implies that PIN1 is not only involved in organ outgrowth, but that it is also necessary for organ separation and positioning. A model is presented in which PIN1 and the local distribution of auxin control phyllotaxis.

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