Presynaptic PICK1 facilitates trafficking of AMPA-receptors between active zone and synaptic vesicle pool

Haglerød, Camilla; Hussain, Suleman; Nakamura, Yasuko; Xia, Jun; Haug, Finn Mogens; Ottersen, Ole Petter; Henley, Jeremy M.; Davanger, Svend

doi:10.1016/j.neuroscience.2016.12.042

Cited by 11 publications

(6 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One study, however, reported that PICK1 did not bind Arp2/3 nor F-actin directly, but was involved in nondirectional organelle motility driven by myosin motors [ 129 ]. PICK1 was also involved in axonal trafficking via its newly identified partner the kinesin-binding protein syntabulin [ 130 ], which might, therefore, act as a motor protein for PICK1 regulation of presynaptic AMPAR trafficking [ 131 , 132 ]. Recently, PICK1 was also shown to interact with a central player in clathrin-mediated endocytosis, the adaptor protein AP2, which bridges cargo proteins and clathrin.…”

Section: Pdz Domain-containing Interactantsmentioning

confidence: 99%

AMPA receptors and their minions: auxiliary proteins in AMPA receptor trafficking

Bissen

Foss

Acker‐Palmer

2019

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

To correctly transfer information, neuronal networks need to continuously adjust their synaptic strength to extrinsic stimuli. This ability, termed synaptic plasticity, is at the heart of their function and is, thus, tightly regulated. In glutamatergic neurons, synaptic strength is controlled by the number and function of AMPA receptors at the postsynapse, which mediate most of the fast excitatory transmission in the central nervous system. Their trafficking to, at, and from the synapse, is, therefore, a key mechanism underlying synaptic plasticity. Intensive research over the last 20 years has revealed the increasing importance of interacting proteins, which accompany AMPA receptors throughout their lifetime and help to refine the temporal and spatial modulation of their trafficking and function. In this review, we discuss the current knowledge about the roles of key partners in regulating AMPA receptor trafficking and focus especially on the movement between the intracellular, extrasynaptic, and synaptic pools. We examine their involvement not only in basal synaptic function, but also in Hebbian and homeostatic plasticity. Included in our review are well-established AMPA receptor interactants such as GRIP1 and PICK1, the classical auxiliary subunits TARP and CNIH, and the newest additions to AMPA receptor native complexes.

show abstract

Section: Pdz Domain-containing Interactantsmentioning

confidence: 99%

AMPA receptors and their minions: auxiliary proteins in AMPA receptor trafficking

Bissen

Foss

Acker‐Palmer

2019

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

show abstract

“…The regulated trafficking occurs upon induction of synaptic plasticity, leading to longlasting postsynaptic modifications. Differently, the constitutive trafficking develops in few minutes, independently on the synaptic activity and it occurs also presynaptically (30,39,40) where it mainly involves AMPA receptors composed of GluA2/ GluA3 subunits (44). Our results clearly indicate that the AMPA autoreceptors in cortical synaptosomes traffic in a constitutive manner, since hindering the GluA2/GRIP1/PICK1 with pep2-SVKI amplifies the (S)AMPA-mediated releasing activity.…”

Section: Discussionmentioning

confidence: 65%

“…The Western blot analysis of the cortical synaptosomal lysates unveiled the presence of the four GluA subunits (Figure 1). Each antibody recognized a component with a mass consistent with the monomeric form of the respective receptor subunit (~110 kDa) (38)(39)(40).…”

Section: The Glutamatergic Synaptosomes Isolated From the Cortex Of Amentioning

confidence: 99%

Antibodies Against the NH2-Terminus of the GluA Subunits Affect the AMPA-Evoked Releasing Activity: The Role of Complement

Cisani¹,

Olivero²,

Usai³

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

Antibodies recognizing the amino-terminal domain of receptor subunit proteins modify the receptor efficiency to controlling transmitter release in isolated nerve endings (e.g., synaptosomes) indirectly confirming their presence in these particles but also allowing to speculate on their subunit composition. Western blot analysis and confocal microscopy unveiled the presence of the GluA1, GluA2, GluA3, and GluA4 receptor subunits in cortical synaptosomes. Functional studies confirmed the presence of presynaptic release-regulating AMPA autoreceptors in these terminals, whose activation releases [3H]D-aspartate ([3H]D-Asp, here used as a marker of glutamate) in a NBQX-dependent manner. The AMPA autoreceptors traffic in a constitutive manner, since entrapping synaptosomes with the pep2-SVKI peptide (which interferes with the GluA2-GRIP1/PICK1 interaction) amplified the AMPA-evoked releasing activity, while the inactive pep2-SVKE peptide was devoid of activity. Incubation of synaptosomes with antibodies recognizing the NH2 terminus of the GluA2 and the GluA3 subunits increased, although to a different extent, the GluA2 and 3 densities in synaptosomal membranes, also amplifying the AMPA-evoked glutamate release in a NBQX-dependent fashion. We then analyzed the releasing activity of complement (1:300) from both treated and untreated synaptosomes and found that the complement-induced overflow occurred in a DL-t-BOA-sensitive, NBQX-insensitive fashion. We hypothesized that anti-GluA/GluA complexes in neuronal membranes could trigger the classic pathway of activation of the complement, modifying its releasing activity. Accordingly, the complement-evoked release of [3H]D-Asp from antiGluA2 and anti-GluA3 antibody treated synaptosomes was significantly increased when compared to untreated terminals and facilitation was prevented by omitting the C1q component of the immunocomplex. Antibodies recognizing the NH2 terminus of the GluA1 or the GluA4 subunits failed to affect both the AMPA and the complement-evoked tritium overflow. Our results suggest the presence of GluA2/GluA3-containing release-regulating AMPA autoreceptors in cortical synaptosomes. Incubation of synaptosomes with commercial anti-GluA2 or anti-GluA3 antibodies amplifies the AMPA-evoked exocytosis of glutamate through a complement-independent pathway, involving an excessive insertion of AMPA autoreceptors in plasma membranes but also affects the complement-dependent releasing activity, by promoting the classic pathway of activation of the immunocomplex. Both events could be relevant to the development of autoimmune diseases typified by an overproduction of anti-GluA subunits.

show abstract

“…The immunogold labeling of sections of the hippocampal CA1 region with an anti-GluA2 antibody confirmed that the GluA2 subunit and PICK1 colocalized at the active zone. Moreover, the overexpression of GFP-PICK1 by the viral infection of organotypic hippocampal cultures significantly reduced the GluA2/3 immunogold labeling within the active zone and in the presynaptic cytoplasm [ 30 ]. These data suggest that PICK1 acts as regulator of presynaptic AMPAR trafficking.…”

Section: Ampar Localization At Presynapsementioning

confidence: 99%

Presynaptic AMPA Receptors in Health and Disease

Zanetti

Regoni

Ratti

et al. 2021

Cells

View full text Add to dashboard Cite

AMPA receptors (AMPARs) are ionotropic glutamate receptors that play a major role in excitatory neurotransmission. AMPARs are located at both presynaptic and postsynaptic plasma membranes. A huge number of studies investigated the role of postsynaptic AMPARs in the normal and abnormal functioning of the mammalian central nervous system (CNS). These studies highlighted that changes in the functional properties or abundance of postsynaptic AMPARs are major mechanisms underlying synaptic plasticity phenomena, providing molecular explanations for the processes of learning and memory. Conversely, the role of AMPARs at presynaptic terminals is as yet poorly clarified. Accruing evidence demonstrates that presynaptic AMPARs can modulate the release of various neurotransmitters. Recent studies also suggest that presynaptic AMPARs may possess double ionotropic-metabotropic features and that they are involved in the local regulation of actin dynamics in both dendritic and axonal compartments. In addition, evidence suggests a key role of presynaptic AMPARs in axonal pathology, in regulation of pain transmission and in the physiology of the auditory system. Thus, it appears that presynaptic AMPARs play an important modulatory role in nerve terminal activity, making them attractive as novel pharmacological targets for a variety of pathological conditions.

show abstract

Presynaptic PICK1 facilitates trafficking of AMPA-receptors between active zone and synaptic vesicle pool

Cited by 11 publications

References 59 publications

AMPA receptors and their minions: auxiliary proteins in AMPA receptor trafficking

AMPA receptors and their minions: auxiliary proteins in AMPA receptor trafficking

Antibodies Against the NH2-Terminus of the GluA Subunits Affect the AMPA-Evoked Releasing Activity: The Role of Complement

Presynaptic AMPA Receptors in Health and Disease

Contact Info

Product

Resources

About