Journal of Biological Chemistry

Kresge, Nicole;Simoni, Robert D.;Hill, Robert L.

doi: 10.1016/s0021-9258(20)87397-9pmid: N/A

Biosynthesis of the Peptidoglycan of Bacterial Cell Walls. VI. Incorporation of l-Threonine into Interpeptide Bridges in Micrococcus roseus (Roberts, W. S. L., Strominger, J. L., and Söll, D. (1968) J. Biol. Chem. 243, 749–756)

doi: 10.1016/s0021-9258(20)87398-0pmid: N/A

Vitamin C is an important antioxidant and enzyme cofactor in both animals and plants. Humans, unable to synthesize the vitamin themselves, compensate by dietary intake, primarily from plants. Plants synthesize the vitamin via the Smirnoff-Wheeler pathway which converts d-glucose to l-ascorbate in a 10-step process. The only step in the pathway that has not been linked to a gene product is the conversion of GDP-l-galactose to l-galactose 1-phosphate.

doi: 10.1016/s0021-9258(20)87399-2pmid: N/A

Immunotherapy against β-amyloid peptide (Aβ) is a leading therapeutic direction for Alzheimer disease. Experimental studies in transgenic mouse models of the disease have demonstrated that Aβ immunization reduces Aβ plaque pathology and improves cognitive function. However, the biological mechanisms by which Aβ antibodies reduce amyloid accumulation in the brain remain unclear.

doi: 10.1016/s0021-9258(20)87400-6pmid: N/A

doi: 10.1016/s0021-9258(20)87329-3pmid: N/A

Kim, Hee-Yong

doi: 10.1074/jbc.r700015200pmid: 17488715

Long-chain polyunsaturated fatty acids are highly enriched in the nervous system. Docosahexaenoic acid (DHA2 ; 22:6n-3), in particular, is the most abundant polyunsaturated fatty acid in the brain and is concentrated in aminophospholipids of cell membranes. Numerous studies have indicated that this concentration of DHA in the nervous system is essential for optimal neuronal and retinal functions (1). Although the underlying mechanisms of its essential function are still not clearly understood, emerging evidence suggests that unique metabolism of DHA in relation to its incorporation into neuronal membrane phospholipids plays an important role.

Hou, Zhibo;Li, Qing;He, Lisheng;Lim, Hui-Ying;Fu, Xinrong;Cheung, Nam Sang;Qi, Donna X.;Qi, Robert Z.

doi: 10.1074/jbc.c700052200pmid: 17491008

<p>Cdk5 and its neuronal activator p35 play an important role in neuronal migration and proper development of the brain cortex. We show that p35 binds directly to α/β-tubulin and microtubules. Microtubule polymers but not the α/β-tubulin heterodimer block p35 interaction with Cdk5 and therefore inhibit Cdk5-p35 activity. p25, a neurotoxin-induced and truncated form of p35, does not have tubulin and microtubule binding activities, and Cdk5-p25 is inert to the inhibitory effect of microtubules. p35 displays strong activity in promoting microtubule assembly and inducing formation of microtubule bundles. Furthermore, microtubules stabilized by p35 are resistant to cold-induced disassembly. In cultured cortical neurons, a significant proportion of p35 localizes to microtubules. When microtubules were isolated from rat brain extracts, p35 co-assembled with microtubules, including cold-stable microtubules. Together, these findings suggest that p35 is a microtubule-associated protein that modulates microtubule dynamics. Also, microtubules play an important role in the control of Cdk5 activation.</p>

Lella, Ravi K.;Sharma, Charu

doi: 10.1074/jbc.c600280200pmid: 17449476

<p>The pathogenesis of tuberculosis is complex and its manifestations diverse, reflecting a lifetime of dynamic interactions between mycobacterial virulence factors and the human immune system. The pathogenic mycobacteria have developed strategies to circumvent the major killing mechanisms employed by macrophages and take advantage of the enclosed environment within its host cell to avoid humoral and cell-mediated immune responses. Secretory proteins play a major role in host-pathogen interactions. The <i>eis</i> (Rv2416c) gene has been identified as a secretory protein, and it has been shown that it enhances intracellular survival of <i>Mycobacterium semgmatis</i> in the macrophage cell line. The main aim of this study was to gain insight into the biological role of Eis in the host. Stimulation of T-cells with Eis recombinant protein of <i>Mycobacterium tuberculosis</i> inhibits Con A-mediated T-cell proliferation <i>in vitro</i>. Treatment of T-cells with Eis inhibits ERK1/2, JAK pathway, and subsequent production of tumor necrosis factor-α and interleukin-4. On the contrary, there is increased production of interferon-γ and interleukin-10, which indicates that immunity in response to Eis treatment is skewed away from a protective T_H1 response and Eis disturbs the cross regulation of T-cells.</p>

Zhu, Wei;Boachie-Adjei, Oheneba;Rawlins, Bernard A.;Frenkel, Baruch;Boskey, Adele L.;Ivashkiv, Lionel B.;Blobel, Carl P.

doi: 10.1074/jbc.m610232200pmid: 17439946

<p>Stromal-derived factor 1 (SDF-1) is a chemokine with important functions in development and postnatal tissue homeostasis. SDF-1 signaling via the G-protein-coupled receptor CXCR4 regulates the recruitment of stem and precursor cells to support tissue-specific repair or regeneration. In this study we examined the contribution of SDF-1 signaling to osteogenic differentiation of mesenchymal C2C12 cells induced by bone morphogenic protein 2 (BMP2). Blocking SDF-1 signaling before BMP2 stimulation by treatment with siRNA, antibodies against SDF-1 or CXCR4, or the G-protein-coupled receptor inhibitor pertussis toxin strongly suppressed BMP2 induction of osteogenic differentiation in C2C12 cells, as evidenced by an early decrease in the expression of the myogenesis inhibitor Id1, the osteogenic master regulators Runx2 and Osx, the osteoblast-associated transcription factors JunB, Plzf, Msx2, and Dlx5, and later of the bone marker proteins osteocalcin and alkaline phosphatase. Similarly, blocking SDF-1/CXCR4 signaling strongly inhibited BMP2-induced osteogenic differentiation of ST2 bone marrow stromal cells. Moreover, we found that the interaction between SDF-1 and BMP2 signaling was mediated via intracellular Smads and MAPK activation. Our data provide the first evidence for a co-requirement of the SDF-1/CXCR4 signaling axis in BMP2-induced osteogenic differentiation of C2C12 and ST2 cells and, thus, uncover a new potential target for modulation of osteogenesis.</p>

Dinkla, Katrin;Nitsche-Schmitz, D. Patric;Barroso, Vanessa;Reissmann, Silvana;Johansson, Helena M.;Frick, Inga-Maria;Rohde, Manfred;Chhatwal, Gursharan S.

doi: 10.1074/jbc.m701047200pmid: 17452321

<p>Acute rheumatic fever is a serious autoimmune sequela of pharyngitis caused by certain group A streptococci. One mechanism applied by streptococcal strains capable of causing acute rheumatic fever is formation of an autoantigenic complex with human collagen IV. In some geographic regions with a high incidence of acute rheumatic fever pharyngeal carriage of group C and group G streptococci prevails. Examination of such strains revealed the presence of M-like surface proteins that bind human collagen. Using a peptide array and recombinant proteins with targeted amino acid substitutions, we could demonstrate that formation of collagen complexes during streptococcal infections depends on an octapeptide motif, which is present in collagen binding M and M-like proteins of different β-hemolytic streptococcal species. Mice immunized with streptococcal proteins that contain the collagen binding octapeptide motif developed high serum titers of anti-collagen antibodies. In sera of rheumatic fever patients such a collagen autoimmune response was accompanied by specific reactivity against the collagen-binding proteins, linking the observed effect to clinical cases. Taken together, the data demonstrate that the identified octapeptide motif through its action on collagen plays a crucial role in the pathogenesis of rheumatic fever. Eradication of streptococci that express proteins with the collagen binding motif appears advisable for controlling rheumatic fever.</p>