Zhu Etal Research Articles

The Kindlin Outside Connection

Transmembrane integrin bridges the extracellular and intracellular environments and is activated by focal adhesion proteins, talin and kindlin. Activated integrin engages ligands from the extracellular matrix and controls intracellular responses. In this issue of Structure, Zhu etal. (2019) describe an initial step involving recruitment of paxillin by ubiquitin-like kindlin-2 domain.

Sunlight Brightens Learning and Memory

Sunlight can alter mood, behavior, and cognition, but the cellular basis of this phenomenon remains to be fully elucidated. In this issue of Cell, Zhu etal. shed light on a UV-dependent metabolic pathway that leads to increased synaptic release of glutamate and enhanced motor learning and memory in mice.

Tomato Multiomics Reveals Consequences of Crop Domestication and Improvement

Genome-scale analyses of variation, gene expression, and metabolite accumulation in ancestral, early domesticates, and modern tomatoes by Zhu etal. identify genes underlying fruit chemistry and demonstrate that alleles affecting metabolic quality have been bred into modern varieties as a result of linkage drag. Similar metabolic hitchhikers are likely ubiquitous in other domesticated species.

The Yolk Sac Feeds Pancreatic Tumors

In this issue of Immunity, Zhu etal. (2017) report that tumor-associated macrophages in a mouse model ofpancreatic ductal adenocarcinoma (PDAC) originate from both the yolk sac (YS) and bone marrow. Differential ablation of these populations indicates that only the YS-derived macrophages promote PDAC progression and growth.

HO-2 Pockets Myristoylated Gag

Membrane binding of viral and cellular N-myristoylated proteins can be regulated by selectively sequestering myristate. In this issue of Cell Host & Microbe, Zhu etal. (2017) report on a myristate binding site within the cellular protein heme oxygenase-2 that acts as a trap to inhibit N-myristoylated protein function.

WASP and WAVE Team Up at the Leading Edge

Arp2/3-dependent branched actin networks drive membrane protrusions, with WAVE being recognized as the critical Arp2/3 activator in this process. In this issue of Developmental Cell, Zhu etal. (2016) demonstrate that WASP, an Arp2/3 activator mostly involved in endocytosis, collaborates with WAVE to promote migration of neuroblasts in Caenorhabditis elegans.

Beige Communication through Gap Junctions and Adaption by Autophagy

How thermogenic stimuli activate and control beige adipocytes is not fully understood. In this issue, Zhu etal. (2016) and Altshuler-Keylin etal. (2016) provide insights into these important issues by demonstrating roles for connexin 43 (Cx43) atg5 and atg12 in signal propagation and phenotypic adaptation in beige adipocytes.

From Worms to Targeting Virulence Factors

Rising antibiotic resistance means that alternative antibacterial strategies are sorely needed. In this issue, Zhu etal. (2015) report the use of a Caenorhabditis elegans model to validate the Pseudomonas aeruginosa virulence factor LasB as a potential therapeutic target and to identify a LasB inhibitor with invivo efficacy.

Time Delay Properties of a Fabry-Pérot Interferometer

The time delay properties of a Fabry-Pérot interferometer are investigated.We found that the group velocity of light through a Fabry-Pérotinterferometer can be reduced to 10-4 of the light speed in vacuum andthe time delay is 210 ns, when the reflectivity is 0.999 and the distancebetween two mirrors is 1 cm. The system is analogous to the recentlyproposed one-dimensional photonic band-gap structures with a defect [Zhuet al. Opt. Commun. 174(2000)139].

What prevents intermolecular V(D)J recombination?

Generation of a highly diverse repertoire of T-cell receptor (TCR) and immunoglobulin (Ig) molecules is ofparamount importance to the immune system. This task isaccomplished through a site-specific DNA rearrangement mechanism, V(D)J recombination, that assemblesthe genes encoding the antigen-binding regions of theseimmune receptor molecules from a large library of genesegments (termed V, D, and J elements) that are separatedin the germ line by variable lengths of noncoding DNA.The same mechanism is used for rearrangement of Iggenes (in developing B lymphocytes) and TCR genes (indeveloping T lymphocytes). Each gene segment isflanked by a recombination signal sequence (RSS), whichconsists of conserved heptamer and nonamer elementsseparated by either 12 or 23 nucleotides of nonconservedDNA sequence. Efficient rearrangement requires oneRSS of each spacer length (a restriction termed the 12/23rule) (Eastman et al. 1996; Steen et al. 1996; van Gent etal. 1996). Rearrangement is initiated by binding of the recombinase proteins, RAG-1 and RAG-2, to the RSS (Fig.1). Formation of a DNA-protein complex containing theRAG proteins bound to a 12-23 RSS pair (a synapticcomplex) is followed by DNA cleavage, which introduces double-strand breaks (DSBs) precisely betweeneach RSS and its adjacent coding element. Cleavage produces two types of broken ends: blunt signal ends, whichterminate in the RSS, and covalently closed (hairpin)coding ends. Joining of these ends requires participationof the machinery used for DSB repair, including components of the DNA-dependent protein kinase (DNA-PK),and generates two types of recombinant junctions: signaljoints and coding joints, respectively (for review, seeLewis 1994; Grawunder et al. 1998). In vivo experimentssuggest that after cleavage, all four ends remain associated in a postcleavage complex (Lewis et al. 1988; Zhu etal. 1996). However, recent in vitro work suggests that thesignal ends are more stably bound to the RAG proteinsthan the coding ends (Hiom and Gellert 1998). The stepsinvolved in end processing and joining and the roles ofDSB repair factors remain unclear. In vivo studies suggest that opening of the hairpin coding ends requires several DSB repair factors, including Ku86 and the catalyticsubunit of the DNA-PK, because hairpin-coding ends accumulate in mutant lymphocytes lacking these proteins(Roth et al. 1992; Zhu and Roth 1995; Zhu et al. 1996).The RAG proteins themselves may also play a part in thejoining of coding ends. Both in vitro analysis (Leu et al.1997; Ramsden et al. 1997) and analysis of mutant RAGproteins in vivo (Steen et al. 1999) indicate that the RAGproteins stimulate formation of coding joints. Furthermore, recent work suggests that the RAG proteins are capable of opening hairpins (Besmer et al. 1998). Thus,both the RAG proteins and components of the DSB repairmachinery may participate in coding joint formation...