NCBI Summary:
This gene encodes a protein that belongs to the microtubule-associated protein family. The proteins of this family are thought to be involved in microtubule assembly, which is an essential step in neurogenesis. The products of similar genes in rat and mouse are neuron-specific cytoskeletal proteins that are enriched in dentrites, implicating a role in determining and stabilizing dentritic shape during neuron development. A number of alternatively spliced variants encoding distinct isoforms have been described. [provided by RefSeq, Jan 2010]
Dephosphorylation of MAP2D enhances its binding to vimentin in preovulatory ovarian granulosa cells. Flynn MP et al. (2016) Preovulatory granulosa cells express microtubule-associated protein(MAP) 2D. Luteinizing hormone(LH)/choriogonadotropin(CG) receptor activation by human(h) CG promotes dephosphorylation of MAP2D on Thr256/Thr259. We sought to evaluate the association of MAP2D with the cytoskeleton and the effect of hCG on this association. MAP2D partially co-localizes by confocal immunofluorescence microscopy with the vimentin intermediate filament and microtubule cytoskeletons in naive cells. In vitro binding studies show that MAP2D binds directly to vimentin and β-tubulin. Phosphorylation of recombinant MAP2D on Thr256/Thr259 that mimics the phosphorylation status of MAP2D in naive cells reduces binding of MAP2D to vimentin and tubulin 2- and 3-fold, respectively. hCG promotes PKA-dependent phosphorylation of vimentin(Ser32/Ser38), increased binding of vimentin to MAP2D, and contraction of granulosa cells with reorganization of vimentin filaments and MAP2D from the periphery into a thickened layer surrounding the nucleus and into prominent cellular extensions. Chemical disruption of vimentin filament organization increased progesterone production. Together these results suggest that hCG-stimulated dephosphorylation of MAP2D at Thr256/Thr259, phosphorylation of vimentin at Ser38/Ser72, and resulting enhanced binding of MAP2D to vimentin may contribute to the progesterone synthetic response required for ovulation.//////////////////
Expression regulated by
FSH, LH
Comment
LUTEINIZING HORMONE RECEPTOR ACTIVATION IN OVARIAN GRANULOSA CELLS PROMOTES PROTEIN KINASE A-DEPENDENT DEPHOSPHORYLATION OF MAP2D. Flynn MP et al. The actions of luteinizing hormone (LH) to induce ovulation and luteinization of preovulatory follicles are mediated principally by activation of cAMP-dependent protein kinase (PKA) in granulosa cells. PKA activity is targeted to specific locations in many cells by A-kinase anchoring proteins (AKAPs). We previously showed that follicle-stimulating hormone (FSH) induces expression of microtubule-associated protein (MAP) 2D, an 80-kDa AKAP, in rat granulosa cells, and that MAP2D co-immunoprecipitates with PKA regulatory subunits in these cells. Here we report a rapid and targeted dephosphorylation of MAP2D at Thr256/Thr259 after treatment with human chorionic gonadotropin (hCG), an LH receptor agonist. This event is mimicked by treatment with forskolin or a cAMP analog and is blocked by the PKA inhibitor myristoylated-PKI, indicating a role for cAMP and PKA signaling in phospho-regulation of granulosa cell MAP2D. Furthermore, we show that Thr256/Thr259 dephosphorylation is blocked by the protein phosphatase 2A (PP2A) inhibitor okadaic acid and demonstrate interactions between MAP2D and PP2A by co-immunoprecipitation and microcystin-agarose pulldown. We also show that MAP2D interacts with glycogen synthase kinase (GSK) 3beta and is phosphorylated at Thr256/Thr259 by this kinase in the basal state. Increased phosphorylation of GSK3beta at Ser9 and the PP2A B56delta subunit at Ser566 is observed after treatment with hCG and appears to result in LH receptor-mediated inhibition of GSK3beta and activation of PP2A, respectively. Taken together, these results show that the phosphorylation status of the AKAP MAP2D is acutely regulated by LH receptor-mediated modulation of kinase and phosphatase activities via PKA.
Ovarian localization
Granulosa, Luteal cells
Comment
Neuronal microtubule-associated protein 2D is a dual A-kinase anchoring protein expressed in rat ovarian granulosa cells.
Salvador LM, et al 2004 .
A Kinase Anchoring Proteins (AKAPs) function to target protein kinase A (PKA) to specific locations within the cell. AKAPs are functionally identified by their ability to bind the type II regulatory subunits (RII) of PKA in an in vitro overlay assay. The authors previously showed that follicle stimulating hormone (FSH) induces the expression of an 80 kDa AKAP (AKAP 80) in ovarian granulosa cells as they mature from a preantral to a preovulatory phenotype. In this report they identify AKAP 80 as microtubule associated protein (MAP) 2D, a low molecular weight splice variant of the neuronal MAP2 protein. MAP2D is induced in granulosa cells by dexamethasone and by FSH in a time-dependent manner that mimics that of AKAP 80, and immunoprecipitation of MAP2D depletes extracts of AKAP 80. MAP2D is the only MAP2 protein present in ovaries and is localized to granulosa cells of preovulatory follicles and to luteal cells. MAP2D is concentrated at the Golgi apparatus along with RI and RII, and based on coimmunoprecipitation results, appears to bind both RI and RII in granulosa cells. Reduced expression of MAP2D resulting from treatment of granulosa cells with antisense oligonucleotides to MAP2 inhibited the phosphorylation of cAMP response element binding protein. These results suggest that this classic neuronal RII AKAP is a dual RI/RII AKAP that performs unique functions in ovarian granulosa cells which contribute to the preovulatory phenotype.