Aberrant cell signaling in response to secreted growth factors has been linked to the development of multiple diseases, including cancer. As such, understanding mechanisms that control growth factor availability and receptor-growth factor interaction is vital. Dually modified transmembrane proteoglycans (DMTPs), which are classified as cell surface macromolecules composed of a core protein decorated with covalently linked heparan sulfated (HS) and/or chondroitin sulfated (CS) glycosaminoglycan (GAG) chains, provide one type of regulatory mechanism. Specifically, DMTPs betaglycan and syndecan-1 (SDC1) play crucial roles in modulating key cell signaling pathways, such as Wnt, transforming growth factor-β and fibroblast growth factor signaling, to affect epithelial cell biology and cancer progression. This review outlines current and potential functions for betaglycan and SDC1, with an emphasis on comparing individual roles for HS and CS modified DMTPs. We highlight the mutual dependence of DMTPs' GAG chains and core proteins and provide comprehensive knowledge on how these DMTPs, through regulation of ligand availability and receptor internalization, control cell signaling pathways involved in development and disease.

Inhibition of Cdh1-APC decreases protein synthesis in cortical neurons Cdh1 interacts with translational machinery including stress granule proteinsCdh1-APC regulates the formation of stress granules in neurons through FMRP Cdh1-APC has a dual role in protein homeostasis

The Drosophila polyadenosine RNA binding protein Nab2, which is orthologous to a human protein lost in a form of inherited intellectual disability, controls adult locomotion, axon projection, dendritic arborization, and memory through a largely undefined set of target RNAs. Here, we show a specific role for Nab2 in regulating splicing of ~150 exons/introns in the head transcriptome and focus on retention of a male-specific exon in the sex determination factor Sex-lethal (Sxl) that is enriched in female neurons. Previous studies have revealed that this splicing event is regulated in females by N6-methyladenosine (m6A) modification by the Mettl3 complex. At a molecular level, Nab2 associates with Sxl pre-mRNA in neurons and limits Sxl m6A methylation at specific sites. In parallel, reducing expression of the Mettl3, Mettl3 complex components, or the m6A reader Ythdc1 rescues mutant phenotypes in Nab2 flies. Overall, these data identify Nab2 as an inhibitor of m6A methylation and imply significant overlap between Nab2 and Mettl3 regulated RNAs in neuronal tissue.

The goal of this article is to provide guidance for those who have decided to apply to graduate school with the plan to obtain a PhD in biomedical science. Choosing an appropriate graduate school and program can seem like a daunting choice. There are numerous graduate training programs that offer excellent training with multiple specific program choices at any given institution. Thus, identifying a program that provides an optimal training environment, which aligns with the applicant's training and career goals, can be daunting. There is no single training program that is ideal for all applicants, and, fortunately, there is no sole perfect place for any individual applicant to obtain a PhD. This article presents points to consider at multiple phases of this process as collected from the authors, including a senior faculty member, a junior faculty member, and four current graduate students who all made different choices for their graduate training (Fig. 1). In Phase I of the process, the vast number of choices must be culled to a reasonable number of schools/programs for the initial application. This is one of the most challenging steps because the number of training programs is very large, and most applicants will rely primarily on information readily available on the internet. Phase II is the exciting stage of visiting the program for an interview where you can ask questions and get a feel for the place. Finally, Phase III suggests information to collect following the interview when comparing choices and making a final decision. While the process may feel long and can be stressful, the good news is that making informed decisions along the way should result in multiple options that can support excellent training and career development.

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