Kalirin, a GDP/GTP Exchange Factor of the Dbl Family, Is Localized to Nerve, Muscle, and Endocrine Tissue During Embryonic Rat Development

Hansel, Donna E.; Quinones, Mercedes; Ronnett, Gabriele V.; Eipper, Betty A.

doi:10.1177/002215540104900704

Cited by 27 publications

(21 citation statements)

References 36 publications

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“…In addition to a Tyr internalization motif, the cytosolic domain of PAM contains multiple phosphorylation sites (32) as well as sites for interacting with Kalirin and Trio, Rho GDP/GTP exchange factors that affect cytoskeletal organization (53,54). Protein kinase A, protein kinase C, casein kinase II, and P-CIP2 each phosphorylate sites in the cytosolic domain of PAM (32,55).…”

Section: Discussionmentioning

confidence: 99%

Trafficking of a Secretory Granule Membrane Protein Is Sensitive to Copper

Ciccotosto

Mains

et al. 2007

Journal of Biological Chemistry

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We explored the effect of copper availability on the synthesis and trafficking of peptidylglycine ␣-amidating monooxygenase (PAM), an essential cuproenzyme whose catalytic domains function in the lumen of peptide-containing secretory granules. Corticotrope tumor cell lines expressing integral membrane and soluble forms of PAM were depleted of copper using bathocuproinedisulfonic acid or loaded with copper by incubation with CuCl 2 . Depleting cellular copper stimulates basal secretion of soluble enzyme produced by endoproteolytic cleavage of PAM in secretory granules and transit of membrane PAM though the endocytic pathway and back into secretory granules. Unlike many cuproenzymes, lack of copper does not lead to instability of PAM. Copper loading decreases cleavage of PAM in secretory granules, secretion of soluble enzyme, and the return of internalized PAM to secretory granules. The trafficking and stability of the soluble, luminal domain of PAM and truncated membrane PAM lacking a cytosolic domain are not affected by copper availability. Taken together, our data demonstrate a role for copper-sensitive cytosolic machinery in directing endocytosed membrane PAM back to secretory granules or to a degradative pathway. The response of PAM to lack of copper suggests that it facilitates copper homeostasis.

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Section: Discussionmentioning

confidence: 99%

Trafficking of a Secretory Granule Membrane Protein Is Sensitive to Copper

Ciccotosto

Mains

et al. 2007

Journal of Biological Chemistry

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“…Kalirin expression is detectable in a wide array of adult tissues including neurons, endocrine cells, liver, muscle, and heart [2, 20, 21]. In addition, developmentally regulated, tissue specific-Kalirin isoform expression is evident.…”

Section: Tissue Expressionmentioning

confidence: 99%

Kalirin, a Key Player in Synapse Formation, Is Implicated in Human Diseases

Mandela

2012

Neural Plasticity

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Synapse formation is considered to be crucial for learning and memory. Understanding the underlying molecular mechanisms of synapse formation is a key to understanding learning and memory. Kalirin-7, a major isoform of Kalirin in adult rodent brain, is an essential component of mature excitatory synapses. Kalirin-7 interacts with multiple PDZ-domain-containing proteins including PSD95, spinophilin, and GluR1 through its PDZ-binding motif. In cultured hippocampal/cortical neurons, overexpression of Kalirin-7 increases spine density and spine size whereas reduction of endogenous Kalirin-7 expression decreases synapse number, and spine density. In Kalirin-7 knockout mice, spine length, synapse number, and postsynaptic density (PSD) size are decreased in hippocampal CA1 pyramidal neurons; these morphological alterations are accompanied by a deficiency in long-term potentiation (LTP) and a decreased spontaneous excitatory postsynaptic current (sEPSC) frequency. Human Kalirin-7, also known as Duo or Huntingtin-associated protein-interacting protein (HAPIP), is equivalent to rat Kalirin-7. Recent studies show that Kalirin is relevant to many human diseases such as Huntington's Disease, Alzheimer's Disease, ischemic stroke, schizophrenia, depression, and cocaine addiction. This paper summarizes our recent understanding of Kalirin function.

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“…Of these, the Kalirin family of dual RhoGEFs was of special interest for p75-mediated, and TrkA-independent regulation of Rac1 and RhoA, because p75 can activate these GTPases depending on with which receptor it has become associated. We therefore tested whether Kalirin9 and 12 that contain both RhoGEF and RacGEF domains (17) can interact with p75 in vitro using pulldown assays with GST-p75…”

Section: Kalirin9 and 12mentioning

confidence: 99%

The Role of Kalirin9 in p75/Nogo Receptor-mediated RhoA Activation in Cerebellar Granule Neurons

Harrington

Tep

et al. 2008

Journal of Biological Chemistry

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p75 and the Nogo receptor form a signaling unit for myelin inhibitory molecules, with p75 being responsible for RhoA activation. Because p75 lacks the GDP/GTP exchange factor domain, it has remained unclear how p75 activates RhoA. Here, we report that Kalirin9, a dual RhoGEF, binds p75 directly and regulates p75-Nogo receptor-dependent RhoA activation and neurite inhibition in response to myelin-associated glycoprotein. The region of p75 that Kalirin9 binds includes its mastoparan-like fifth helix, which was shown to recruit RhoGDI-RhoA. As predicted from the presence of a shared binding site, we found that Kalirin9 competes with RhoGDI for p75 binding in a dose-dependent manner in vitro. In line with these data, myelinassociated glycoprotein addition to cerebellar granule neurons resulted in a reduction in the association of Kalirin9 with p75, and a simultaneous increase in the binding of RhoGDI to p75. These results reveal a mechanism by which the fifth helix of p75 regulates RhoA activation.

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Kalirin, a GDP/GTP Exchange Factor of the Dbl Family, Is Localized to Nerve, Muscle, and Endocrine Tissue During Embryonic Rat Development

Cited by 27 publications

References 36 publications

Trafficking of a Secretory Granule Membrane Protein Is Sensitive to Copper

Trafficking of a Secretory Granule Membrane Protein Is Sensitive to Copper

Kalirin, a Key Player in Synapse Formation, Is Implicated in Human Diseases

The Role of Kalirin9 in p75/Nogo Receptor-mediated RhoA Activation in Cerebellar Granule Neurons

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