Disease relevance of PLXNA1

• We here report that human malignant glioma cell lines express neuropilins 1 and 2 mRNA and protein, as well as either plexin A1, A2, or B1 [1].
• Nucleotide variation analysis does not support a causal role for plexin-A1 in hereditary congenital facial paresis [2].
• NOVP chemotherapy for Hodgkin's disease transiently induces sperm aneuploidies associated with the major clinical aneuploidy syndromes involving chromosomes X, Y, 18, and 21 [3].
• NOVP: a novel chemotherapeutic regimen with minimal toxicity for treatment of Hodgkin's disease [4].

High impact information on PLXNA1

• In our study we observed eight male HD patients who were treated with NOVP (Novanthrone, Oncovin, Vinblastine, Prednisone) chemotherapy [5].
• Winberg et al. present evidence that the transmembrane protein Off-track (OTK) interacts biochemically and genetically with Plexin A and is important for Sema 1a repulsive signaling [6].
• Northern blot analysis revealed different expression of the SEX family of genes in fetal tissues, with SEX, OCT, and NOV predominantly expressed in brain, and SEP expressed at highest levels in kidney [7].
• Reducing SEMA3A or NP1 expression by RNA interference or inhibiting plexin-A1 signaling enhanced migration [8].
• Conversely, expression of constitutively active plexin-A1 impaired chemotaxis [8].

Chemical compound and disease context of PLXNA1

• PURPOSE: Because the effects of mitoxantrone on human male fertility were unknown, we determined prospectively the effects of three courses of mitoxantrone (Novantrone), vincristine (Oncovin), vinblastine, prednisone (NOVP) chemotherapy on the potential for fertility of men with Hodgkin's disease (HD) [9].
• To better define the importance of the GS in predicting treatment results in a group of patients treated with uniform therapy, we performed GS prior to treatment in 46 patients with pathologically or clinically staged I-III Hodgkin's disease who received three cycles of NOVP (Novantrone, vincristine, vinblastine, prednisone) followed by XRT [10].
• NOVP has also been reported to produce limited toxicity in this trial and should be considered as an alternative to MOPP or doxorubicin-containing regimens in treatment of patients with early-staged disease and LMA greater than 10 cm [11].

Biological context of PLXNA1

• We have analyzed the expression of Neuropilin-1, Plexin-A1, and Semaphorin 3A in the above-mentioned tissues on the hypothesis that these molecules could regulate innervation in these organs during gestation [12].
• This chapter describes the optimization of this assay and outlines the subtle differences required to enable Sema3A-Fc and Sema4D-Fc to induce identical collapse phenotypes in COS cells expressing Plexin-A1 and neuropilin-1, or Plexin-B1, respectively [13].
• Using an in vivo model of microglia activation by striatal injection of lipopolysaccharide demonstrated a corresponding upregulation of Plexin-A1 and Neuropilin-1 in activated microglia and enhanced production of Sema3A by stressed adult neurons [14].
• Plexin-A1 can function as a signal transducing subunit for the neuronal neuropilin receptor, and its gene is located in the linkage interval for hereditary congenital facial paresis at chromosome 3q21-q22 (MIM601471), making it an excellent candidate gene for this disorder [2].
• We therefore conclude that it is highly unlikely that Plexin-A1 is involved in the pathogenicity of hereditary congenital facial paresis [2].

Anatomical context of PLXNA1

• Sema3A/Plexin-A1-induced growth cone collapse, for example, requires Rac activity, which is a surprising result given that this GTPase is usually associated with membrane protrusions [15].
• We show here that Sema3A-induced collapse of COS-7 cells expressing Plexin-A1 also requires Rac but not Rho activity and that the cytoplasmic tail of Plexin-A1 interacts directly with activated Rac [15].
• RanBPM has the potential to link Plexin-A receptors to retrograde transport and microtubule function in axonal guidance [16].
• During mouse embryogenesis, the murine ortholog of plexin-A1 gene showed restricted spatial and temporal expression in the hindbrain, consistent with a role in cell body movement, or axonal guidance during facial nerve development [2].
• Differentiated podocytes expressed 2-4-fold higher plexin A1, A2, and A3 mRNA levels than undifferentiated podocytes [17].

Associations of PLXNA1 with chemical compounds

• The impact of radiation therapy, given after mitoxantrone, vincristine, vinblastine, and prednisone (NOVP) chemotherapy, on sperm production is the focus of this study [18].
• All patients initially received three cycles of a novel chemotherapeutic regimen combining Novantrone (mitoxantrone, American Cyanamid Company), vincristine, vinblastine, and prednisone (NOVP) [4].
• PATIENTS: Serial semen analyses were performed on 34 patients with HD Stages I-III before NOVP chemotherapy, after chemotherapy prior to radiation, and after radiation therapy [18].
• Recently, the combination chemotherapy Novantrone, Oncovin, Velban, Prednisone [NOVP] was developed by The University of Texas M [19].
• Preliminary clinical results show that NOVP is as effective as the traditional Mechlorethamine, Oncovin, Procarbazine, Prednisone [MOPP] regimen in achieving remission, but with fewer side-effects [19].

Regulatory relationships of PLXNA1

• Recruitment of active Rnd1 is sufficient to trigger signaling by Plexin-A1, even in the absence of Sema3A, and initiates cytoskeletal collapse by activating its cytoplasmic domain [20].

Other interactions of PLXNA1

• Thus, the antagonism of two GTPases regulates the activity of the Sema3A receptor, and activation by Rnd1 appears to be an essential step in signaling by Plexin-A1 [20].
• CIITA also regulates the gene expression of plexna-1, which encodes a semaphorin receptor, plexin-A1, that might be involved in the interaction with T-cells through an unknown ligand for plexin-A1 [21].
• Reducing plexin-A1 expression with shRNA greatly reduced actin polarization as well as Rho activation without affecting Rac or Cdc42 activation [22].

Analytical, diagnostic and therapeutic context of PLXNA1

• Sequence analysis of the plexin-A1 gene in patients from the 3q21-q22-linked hereditary congenital facial paresis family revealed several nucleotide changes [2].
• After the combination of NOVP plus abdominal radiotherapy, sperm counts and motility were restored in most patients to pretreatment levels, which were compatible with normal fertility [9].
• Sperm counts declined significantly within 1 month after the start of NOVP chemotherapy [9].
• Induced effects did not persist to 1-2 years after treatment, suggesting that persistent spermatogonial stem cells were not sensitive to NOVP [3].
• NOVP is an effective adjuvant chemotherapy regimen for inducing responses, with minimal toxicity, prior to definitive radiotherapy for patients with early-staged Hodgkin's disease [4].

References