The schizophrenic faces of PICK1

Dev, Kumlesh K.; Henley, Jeremy M.

doi:10.1016/j.tips.2006.09.007

Cited by 48 publications

(44 citation statements)

References 79 publications

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“…Recently, disrupted endocytic trafficking found in many brain disorders has attracted much attention. Defective endocytosis is implicated in schizophrenia and bipolar disorder (Dev and Henley, 2006; Schubert et al, 2012), impaired endosomal sorting is linked to Down’s syndrome (Wang et al, 2013) and altered endosomal recycling is associated with autism (Mejias et al, 2011). These discoveries together suggest a critical role for endocytic trafficking in human cognition, although the underlying molecular mechanisms remain largely unknown.…”

Section: Discussionmentioning

confidence: 99%

GRASP1 Regulates Synaptic Plasticity and Learning through Endosomal Recycling of AMPA Receptors

Chiu

Diering

et al. 2017

Neuron

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Summary Learning depends on experience-dependent modification of synaptic efficacy and neuronal connectivity in the brain. We provide direct evidence for physiological roles of the recycling endosome protein GRASP1 in glutamatergic synapse function and animal behavior. Mice lacking GRASP1 showed abnormal excitatory synapse number, synaptic plasticity and hippocampal-dependent learning and memory due to a failure in learning-induced synaptic AMPAR incorporation. We identified two GRASP1 point mutations from intellectual disability (ID) patients that showed convergent disruptive effects on AMPAR recycling and glutamate uncaging-induced structural and functional plasticity. Wild-type GRASP1, but not ID mutants, rescues spine loss in hippocampal CA1 neurons of Grasp1 knockout mice. Together, these results demonstrate a requirement for normal recycling endosome function in AMPAR-dependent synaptic function and neuronal connectivity in vivo, and suggest a potential role for GRASP1 in the pathophysiology of human cognitive disorders.

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Section: Discussionmentioning

confidence: 99%

GRASP1 Regulates Synaptic Plasticity and Learning through Endosomal Recycling of AMPA Receptors

Chiu

Diering

et al. 2017

Neuron

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“…Brains of SCZ patients have lower levels of PICK1 and other proteins critical for AMPAR function and trafficking, including GluA2 and stargazin (Beneyto & Meador-Woodruff 2006). PICK1 additionally interacts with multiple proteins implicated in SCZ, including SR and ZDHHC8 (Dev & Henley 2006).…”

Section: Schizophreniamentioning

confidence: 99%

Glutamate Synapses in Human Cognitive Disorders

Volk

Chiu

Sharma

et al. 2015

Annu. Rev. Neurosci.

223

179

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Accumulating data, including those from large genetic association studies, indicate that alterations in glutamatergic synapse structure and function represent a common underlying pathology in many symptomatically distinct cognitive disorders. In this review, we discuss evidence from human genetic studies and data from animal models supporting a role for aberrant glutamatergic synapse function in the etiology of intellectual disability (ID), autism spectrum disorder (ASD), and schizophrenia (SCZ), neurodevelopmental disorders that comprise a significant proportion of human cognitive disease and exact a substantial financial and social burden. The varied manifestations of impaired perceptual processing, executive function, social interaction, communication, and/or intellectual ability in ID, ASD, and SCZ appear to emerge from altered neural microstructure, function, and/or wiring rather than gross changes in neuron number or morphology. Here, we review evidence that these disorders may share a common underlying neuropathy: altered excitatory synapse function. We focus on the most promising candidate genes affecting glutamatergic synapse function, highlighting the likely disease-relevant functional consequences of each. We first present a brief overview of glutamatergic synapses and then explore the genetic and phenotypic evidence for altered glutamate signaling in ID, ASD, and SCZ.

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“…PICK1 is widely expressed in brain, testis, heart, lung, liver, kidney and muscle [12]. Its abnormal expression in brain has been linked to schizophrenia and other mental disorders [21][22][23]. However, the significance of PICK1 in other organs has not been well characterized.…”

Section: Introductionmentioning

confidence: 99%

PICK1 promotes caveolin-dependent degradation of TGF-β type I receptor

Zhao

Wang

et al. 2012

Cell Res

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Protein that interacts with C kinase 1 (PICK1) is a critical mediator of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking in neural synapses. However, its ubiquitous expression suggests that it may have other non-neural functions. Here we show that PICK1 antagonizes transforming growth factor beta (TGF-β) signaling by targeting TGF-β type I receptor (TβRI) for degradation. Biochemical analyses reveal that PICK1 directly interacts with the C-terminus of TβRI via its PDZ domain and acts as a scaffold protein to enhance the interaction between TβRI and caveolin-1, leading to enhanced lipid raft/caveolae localization. Therefore, PICK1 increases caveolin-mediated endocytosis, ubiquitination and degradation of TβRI. Moreover, a negative correlation between PICK1 expression and TβRI or phospho-Smad2 levels is observed in human breast tumors, indicating that PICK1 may participate in breast cancer development through inhibition of TGF-β signaling. Our findings reveal a non-neural function of PICK1 as an important negative regulator of TGF-β signaling.

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The schizophrenic faces of PICK1

Cited by 48 publications

References 79 publications

GRASP1 Regulates Synaptic Plasticity and Learning through Endosomal Recycling of AMPA Receptors

GRASP1 Regulates Synaptic Plasticity and Learning through Endosomal Recycling of AMPA Receptors

Glutamate Synapses in Human Cognitive Disorders

PICK1 promotes caveolin-dependent degradation of TGF-β type I receptor

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