Somatostatin receptor subtype 1 is a PDZ ligand for synapse-associated protein 97 and a potential regulator of growth cone dynamics

Chunlin Cai, H Li, A Kangasniemi, Tero Pihlajamaa, Lotta Ossowski von, Katja Maria Kerkelä, S Schulz, Claudio Rivera Baeza, Kari Keinänen

Research output: Contribution to journalArticleScientificpeer-review

Abstract

We report that somatostatin receptor subtype 1 (sst1) associates in vivo and in vitro with synapse-associated protein SAP) 97, a membrane-associated guanylate kinase homolog implicated as a scaffolding protein in the structural organization of specialized membrane complexes in various tissues, including the CNS. SAP97 and sst1 were coimmunoprecipitated from rodent brain and from transfected human embryonic kidney (HEK) 293 cells, and pull-down experiments demonstrated that the interaction is dependent on the class I PDZ binding motif in sst1 carboxyterminus. Calorimetric titration indicated that the postsynaptic density-95/discs large/zona occludens-1 (PDZ) 2 domain of SAP97 provides the main contribution to the interaction. We noticed substantial sst1 immunoreactivity in differentiating cortical neurons in culture which declined as the cultures matured. The sst1 immunoreactivity extended, together with SAP97 to neuronal growth cones. Somatostatin (1 mu M) triggered retraction of the filopodia and lamellipodia in the growth cones. This growth cone collapse was enhanced by overexpression of green fluorescent protein-tagged sst1, whereas sst1 mutant lacking the PDZ binding motif had no effect. These findings suggest a role for somatostatin signaling In the regulation of growth cone stability, which may involve PDZ domain proteins Interacting with sst1 and/or other somatostatin receptors. Consistent with a developmental role, sst1 immunoreactivity was present transiently in the developing mouse cortex, peaking at postnatal day 5 and declining thereafter to low levels in the adult cortex. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.
Original languageEnglish
JournalNeuroscience
Volume157
Issue number4
Pages (from-to)833-843
Number of pages11
ISSN0306-4522
DOIs
Publication statusPublished - 2008
MoE publication typeA1 Journal article-refereed

Cite this

Cai, Chunlin ; Li, H ; Kangasniemi, A ; Pihlajamaa, Tero ; Ossowski von, Lotta ; Kerkelä, Katja Maria ; Schulz, S ; Rivera Baeza, Claudio ; Keinänen, Kari. / Somatostatin receptor subtype 1 is a PDZ ligand for synapse-associated protein 97 and a potential regulator of growth cone dynamics. In: Neuroscience. 2008 ; Vol. 157, No. 4. pp. 833-843.
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abstract = "We report that somatostatin receptor subtype 1 (sst1) associates in vivo and in vitro with synapse-associated protein SAP) 97, a membrane-associated guanylate kinase homolog implicated as a scaffolding protein in the structural organization of specialized membrane complexes in various tissues, including the CNS. SAP97 and sst1 were coimmunoprecipitated from rodent brain and from transfected human embryonic kidney (HEK) 293 cells, and pull-down experiments demonstrated that the interaction is dependent on the class I PDZ binding motif in sst1 carboxyterminus. Calorimetric titration indicated that the postsynaptic density-95/discs large/zona occludens-1 (PDZ) 2 domain of SAP97 provides the main contribution to the interaction. We noticed substantial sst1 immunoreactivity in differentiating cortical neurons in culture which declined as the cultures matured. The sst1 immunoreactivity extended, together with SAP97 to neuronal growth cones. Somatostatin (1 mu M) triggered retraction of the filopodia and lamellipodia in the growth cones. This growth cone collapse was enhanced by overexpression of green fluorescent protein-tagged sst1, whereas sst1 mutant lacking the PDZ binding motif had no effect. These findings suggest a role for somatostatin signaling In the regulation of growth cone stability, which may involve PDZ domain proteins Interacting with sst1 and/or other somatostatin receptors. Consistent with a developmental role, sst1 immunoreactivity was present transiently in the developing mouse cortex, peaking at postnatal day 5 and declining thereafter to low levels in the adult cortex. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.",
author = "Chunlin Cai and H Li and A Kangasniemi and Tero Pihlajamaa and {Ossowski von}, Lotta and Kerkel{\"a}, {Katja Maria} and S Schulz and {Rivera Baeza}, Claudio and Kari Kein{\"a}nen",
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doi = "10.1016/j.neuroscience.2008.09.048",
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Somatostatin receptor subtype 1 is a PDZ ligand for synapse-associated protein 97 and a potential regulator of growth cone dynamics. / Cai, Chunlin; Li, H; Kangasniemi, A; Pihlajamaa, Tero; Ossowski von, Lotta; Kerkelä, Katja Maria; Schulz, S; Rivera Baeza, Claudio; Keinänen, Kari.

In: Neuroscience, Vol. 157, No. 4, 2008, p. 833-843.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Somatostatin receptor subtype 1 is a PDZ ligand for synapse-associated protein 97 and a potential regulator of growth cone dynamics

AU - Cai, Chunlin

AU - Li, H

AU - Kangasniemi, A

AU - Pihlajamaa, Tero

AU - Ossowski von, Lotta

AU - Kerkelä, Katja Maria

AU - Schulz, S

AU - Rivera Baeza, Claudio

AU - Keinänen, Kari

PY - 2008

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N2 - We report that somatostatin receptor subtype 1 (sst1) associates in vivo and in vitro with synapse-associated protein SAP) 97, a membrane-associated guanylate kinase homolog implicated as a scaffolding protein in the structural organization of specialized membrane complexes in various tissues, including the CNS. SAP97 and sst1 were coimmunoprecipitated from rodent brain and from transfected human embryonic kidney (HEK) 293 cells, and pull-down experiments demonstrated that the interaction is dependent on the class I PDZ binding motif in sst1 carboxyterminus. Calorimetric titration indicated that the postsynaptic density-95/discs large/zona occludens-1 (PDZ) 2 domain of SAP97 provides the main contribution to the interaction. We noticed substantial sst1 immunoreactivity in differentiating cortical neurons in culture which declined as the cultures matured. The sst1 immunoreactivity extended, together with SAP97 to neuronal growth cones. Somatostatin (1 mu M) triggered retraction of the filopodia and lamellipodia in the growth cones. This growth cone collapse was enhanced by overexpression of green fluorescent protein-tagged sst1, whereas sst1 mutant lacking the PDZ binding motif had no effect. These findings suggest a role for somatostatin signaling In the regulation of growth cone stability, which may involve PDZ domain proteins Interacting with sst1 and/or other somatostatin receptors. Consistent with a developmental role, sst1 immunoreactivity was present transiently in the developing mouse cortex, peaking at postnatal day 5 and declining thereafter to low levels in the adult cortex. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.

AB - We report that somatostatin receptor subtype 1 (sst1) associates in vivo and in vitro with synapse-associated protein SAP) 97, a membrane-associated guanylate kinase homolog implicated as a scaffolding protein in the structural organization of specialized membrane complexes in various tissues, including the CNS. SAP97 and sst1 were coimmunoprecipitated from rodent brain and from transfected human embryonic kidney (HEK) 293 cells, and pull-down experiments demonstrated that the interaction is dependent on the class I PDZ binding motif in sst1 carboxyterminus. Calorimetric titration indicated that the postsynaptic density-95/discs large/zona occludens-1 (PDZ) 2 domain of SAP97 provides the main contribution to the interaction. We noticed substantial sst1 immunoreactivity in differentiating cortical neurons in culture which declined as the cultures matured. The sst1 immunoreactivity extended, together with SAP97 to neuronal growth cones. Somatostatin (1 mu M) triggered retraction of the filopodia and lamellipodia in the growth cones. This growth cone collapse was enhanced by overexpression of green fluorescent protein-tagged sst1, whereas sst1 mutant lacking the PDZ binding motif had no effect. These findings suggest a role for somatostatin signaling In the regulation of growth cone stability, which may involve PDZ domain proteins Interacting with sst1 and/or other somatostatin receptors. Consistent with a developmental role, sst1 immunoreactivity was present transiently in the developing mouse cortex, peaking at postnatal day 5 and declining thereafter to low levels in the adult cortex. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.

U2 - 10.1016/j.neuroscience.2008.09.048

DO - 10.1016/j.neuroscience.2008.09.048

M3 - Article

VL - 157

SP - 833

EP - 843

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

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