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921.
922.
923.
Windus LC Chehrehasa F Lineburg KE Claxton C Mackay-Sim A Key B St John JA 《Cellular and molecular life sciences : CMLS》2011,68(19):3233-3247
Axons of primary olfactory neurons are intimately associated with olfactory ensheathing cells (OECs) from the olfactory epithelium until the final targeting of axons within the olfactory bulb. However, little is understood about the nature and role of interactions between OECs and axons during development of the olfactory nerve pathway. We have used high resolution time-lapse microscopy to examine the growth and interactions of olfactory axons and OECs in vitro. Transgenic mice expressing fluorescent reporters in primary olfactory axons (OMP-ZsGreen) and ensheathing cells (S100ß-DsRed) enabled us to selectively analyse these cell types in explants of olfactory epithelium. We reveal here that rather than providing only a permissive substrate for axon growth, OECs play an active role in modulating the growth of pioneer olfactory axons. We show that the interactions between OECs and axons were dependent on lamellipodial waves on the shaft of OEC processes. The motility of OECs was mediated by GDNF, which stimulated cell migration and increased the apparent motility of the axons, whereas loss of OECs via laser ablation of the cells inhibited olfactory axon outgrowth. These results demonstrate that the migration of OECs strongly regulates the motility of axons and that stimulation of OEC motility enhances axon extension and growth cone activity. 相似文献
924.
Alemu EA Sjøttem E Outzen H Larsen KB Holm T Bjørkøy G Johansen T 《Cellular and molecular life sciences : CMLS》2011,68(11):1953-1968
The protein kinase C (PKC) family of serine/threonine kinases consists of ten different isoforms grouped into three subfamilies,
denoted classical, novel and atypical PKCs (aPKCs). The aPKCs, PKCι/λ and PKCζ serve important roles during development and
in processes subverted in cancer such as cell and tissue polarity, cell proliferation, differentiation and apoptosis. In an
effort to identify novel interaction partners for aPKCs, we performed a yeast two-hybrid screen with the regulatory domain
of PKCι/λ as bait and identified the Krüppel-like factors family protein TIEG1 as a putative interaction partner for PKCι/λ.
We confirmed the interaction of both aPKCs with TIEG1 in vitro and in cells, and found that both aPKCs phosphorylate the DNA-binding
domain of TIEG1 on two critical residues. Interestingly, the aPKC-mediated phosphorylation of TIEG1 affected its DNA-binding
activity, subnuclear localization and transactivation potential. 相似文献
925.
926.
The maintenance of mucosal barrier equilibrium in the intestine requires a delicate and dynamic balance between enterocyte
loss by apoptosis and the generation of new cells by proliferation from stem cell precursors at the base of the intestinal
crypts. When the balance shifts towards either excessive or insufficient apoptosis, a broad range of gastrointestinal diseases
can manifest. Recent work from a variety of laboratories has provided evidence in support of a role for receptors of the innate
immune system, including Toll-like receptors 2, 4, and 9 as well as the intracellular pathogen recognition receptor NOD2/CARD15,
in the initiation of enterocyte apoptosis. The subsequent induction of enterocyte apoptosis in response to the activation
of these innate immune receptors plays a key role in the development of various intestinal diseases, including necrotizing
enterocolitis, Crohn’s disease, ulcerative colitis, and intestinal cancer. This review will detail the regulatory pathways
that govern enterocyte apoptosis, and will explore the role of the innate immune system in the induction of enterocyte apoptosis
in gastrointestinal disease. 相似文献
927.
Lubka-Pathak M Shah AA Gallozzi M Müller M Zimmermann U Löwenheim H Pfister M Knipper M Blin N Schimmang T 《Cellular and molecular life sciences : CMLS》2011,68(16):2739-2749
Introduction
Tff3 peptide exerts important functions in cytoprotection and restitution of the gastrointestinal (GI) tract epithelia. Moreover, its presence in the rodent inner ear and involvement in the hearing process was demonstrated recently. However, its role in the auditory system still remains elusive. Our previous results showed a deterioration of hearing with age in Tff3-deficient animals.Results
Present detailed analysis of auditory brain stem response (ABR) measurements and immunohistochemical study of selected functional proteins indicated a normal function and phenotype of the cochlea in Tff3 mutants. However, a microarray-based screening of tissue derived from the auditory central nervous system revealed an alteration of securin (Pttg1) and serpina3n expression between wild-type and Tff3 knock-out animals. This was confirmed by qRT-PCR, immunostaining and western blots.Conclusions
We found highly down-regulated Pttg1 and up-regulated serpina3n expression as a consequence of genetically deleting Tff3 in mice, indicating a potential role of these factors during the development of presbyacusis. 相似文献928.
Biological cells harbor a variety of molecular machines that carry out mechanical work at the nanoscale. One of these nanomachines
is the bacterial motor protein SecA which translocates secretory proteins through the protein-conducting membrane channel
SecYEG. SecA converts chemically stored energy in the form of ATP into a mechanical force to drive polypeptide transport through
SecYEG and across the cytoplasmic membrane. In order to accommodate a translocating polypeptide chain and to release transmembrane
segments of membrane proteins into the lipid bilayer, SecYEG needs to open its central channel and the lateral gate. Recent
crystal structures provide a detailed insight into the rearrangements required for channel opening. Here, we review our current
understanding of the mode of operation of the SecA motor protein in concert with the dynamic SecYEG channel. We conclude with
a new model for SecA-mediated protein translocation that unifies previous conflicting data. 相似文献
929.
Yvonne G. J. van Helden Roger W. L. Godschalk Hans J. M. Swarts Peter C. H. Hollman Frederik J. van Schooten Jaap Keijer 《Cellular and molecular life sciences : CMLS》2011,68(3):489-504
Molecular mechanisms triggered by high dietary beta-carotene (BC) intake in lung are largely unknown. We performed microarray
gene expression analysis on lung tissue of BC supplemented beta-carotene 15,15′-monooxygenase 1 knockout (Bcmo1
−/−) mice, which are—like humans—able to accumulate BC. Our main observation was that the genes were regulated in an opposite direction in male and female Bcmo1
−/− mice by BC. The steroid biosynthetic pathway was overrepresented in BC-supplemented male Bcmo1
−/− mice. Testosterone levels were higher after BC supplementation only in Bcmo1
−/− mice, which had, unlike wild-type (Bcmo1
+/+) mice, large variations. We hypothesize that BC possibly affects hormone synthesis or metabolism. Since sex hormones influence
lung cancer risk, these data might contribute to an explanation for the previously found increased lung cancer risk after
BC supplementation (ATBC and CARET studies). Moreover, effects of BC may depend on the presence of frequent human BCMO1 polymorphisms, since these effects were not found in wild-type mice. 相似文献
930.
The skin is our primary shield against microbial pathogens and has evolved innate and adaptive strategies to enhance immunity
in response to injury or microbial insult. The study of antimicrobial peptide (AMP) production in mammalian skin has revealed
several of the elegant strategies that AMPs use to prevent infection. AMPs are inducible by both infection and injury and
protect the host by directly killing pathogens and/or acting as multifunctional effector molecules that trigger cellular responses
to aid in the anti-infective and repair response. Depending on the specific AMP, these molecules can influence cytokine production,
cell migration, cell proliferation, differentiation, angiogenesis and wound healing. Abnormal production of AMPs has been
associated with the pathogenesis of several cutaneous diseases and plays a role in determining a patient’s susceptibility
to pathogens. This review will discuss current research on the regulation and function of AMPs in the skin and in skin disorders. 相似文献