Tunneling nanotubes (TNTs) are thin membranous tubes that interconnect cells and enable transfer of cellular components over long distances. TNTs have an actin core surrounded by a lipid bilayer and can be formed through filopodia-like protrusions or after cell collision. They transport organelles, vesicles, proteins, and pathogens between cells and play roles in signaling, immune response, embryogenesis, and cancer progression. TNTs allow spread of pathogens like viruses and bacteria and transfer of proteins involved in diseases such as Parkinson's.

2. Tunneling Nanotubes:

3. • Seminar topic: Tunneling Nanotubes
• Submitted to: Rabia Saba
• Submitted by: Aqeel Raza Jaffri
• Roll No:
• Class: BS.Zoology ss (Semester 7)
University of Sargodha, Sub-campus Bhakkar

4. CONTENTS
• What are Tunneling Nanotubes?
• Purpose
• Other names of TNTs.
• Other structures like TNTs.
• History.
• Structure .
• Functions .
• Formation
• TNTs in cancer cells.
• TNTs in bacterial cells

5. Tunneling Nanotubes
• A tunneling Nanotubes or membrane
Nanotubes is a term that has been applied to
protrusions that extend from the plasma
membrane that enable different animal cells
to touch over long distances,
• Tunneling Nanotubes (TNTs) are recently
discovered thin membranous tubes that
interconnect cells.

6. Purpose:
• The purpose of this study was to investigate
the role of tunneling nanotubes (TNTs) as
unique intercellular conduits capable of
propagating a long-range form of the
bystander effect following oncolytic viral
infection of cancer cells.

7. • TNTs are long, fine, nonadherent actin-
based cytoplasmic extensions capable of
forming direct connections between cells at
both close and distant proximity

8. • Tunneling Nanotubes between neurons
enable the spread of Parkinson's disease via
lysosomes

9. • Scientists have demonstrated the role of
lysosomal vesicles in transporting α-
synuclein aggregates, responsible for
Parkinson's and other neurodegenerative
diseases, between neurons. These proteins
move from one neuron to the next in
lysosomal vesicles which travel along the
"tunneling nanotubes" between cells.

10. Other names of TNTs:
• Tunneling Nanotubes are the protrusions that
extend from plasma membrane so these are
also called as “Membrane Nanotubes”.
• These nanotubes are also called as “
Intercellular nanotubes”

11. Other structures like TNTs:
• Other structures that perform similar
functions like TNTs are:
• Gap- Junctions.
• Plasmodesmata.
• Cytonemes.

12. Gap Junctions:
• Intercellular channels.
• Permit passage of ions and small molecules.
• Most abundant in cardiac and smooth
muscles.
• Coordinate muscle cell contraction.

13. Plasmodesmata:
• Plasmodesmata are protoplasmic strands that
connects the protoplasts of neighboring cells.
• Diameter is 40-50nm.
• Easily seen in endosperm of seeds such as
Phoenix and Aesculus.

14. Cytonemes:
• Cytonemes are thin cellular projections that
are specialized for exchange of signaling
proteins between cells.
• Cytonemes emanate from cells that make
signaling proteins extending directly to cells
that receive signaling proteins.

15. Cytonemes and tunneling nanotubules
in cell–cell communication

16. TNTs and EVs: Synergies in Cargo Transfer and
Intercellular Communication

17. • Tunneling nanotubes and extracellular
vesicle mediated intercellular
communication and cargo transfer.
Tunneling nanotubes transport cellular
organelles such as mitochondria and
lysosomes, as well as viruses, viral genome,
lipid droplets, intera-cellular vesicles and
Ca2+ and electrical signals.

18. History:
• In 2004, Rustom and colleagues reported in
vitro findings of a thin structure connecting
single cells overlong distances.
• TNTs were first characterized between Rat
PC12 cells.
• These thin structures facilitated transfer of
membrane vesicles.
• Furthermore, TNTs have been shown to be
involved in the spread of pathogens.

19. Structure of TNTs:
• The structure coined a tunneling nanotubes,
was hovering above the substrate.
• It contained a straight, continuous actin rod
enclosed in a lipid bilayer.
• No TNT-specific protein markers are known.
• The property that most clearly separates TNTs
from other cellular protrusions in vitro is their
straight, bridge like structure, interconnecting
cell pairs.

20. Structure of TNTs:
• Length of TNTS displays large variation
depending on cells.
• TNT connecting T cells were reported to have
an average length of 22um.
• Whereas in PC12 cells, the length was found to
be much less.
• TNTs lengths can vary as connected cells
migrate and distances between them change.

21. Structure of TNTs:
• PC12 cells diameter range is 50-200nm.
• Some TNTs reach thickness of over 700nm,
which could be due to additional components
inside, such as microtubules.

22. Functions of TNTs:
• TNTs maybe involved in following functions:
• Spread of viral and bacterial pathogens.
• Transfer of cellular proteins responsible for
disease.
• Calcium ions movement.
• Mitochondria exchange.

23. Formation of TNTs:
Two mechanisms are known for formation of
TNTs:
• Filopodia like protrusions.
• After collision between two cells

24. Tunneling nanotubes in HIV-1 spread

25. TNTs in cancer cells:
• Using light microscopy TNTs were
demonstrated between co-cultured RT4 and
T24 bladder cancer cells.
• Spontaneous unidirectional transfer of
mitochondria from T24 to RT4 cells.
• This transfer was followed by an increase in
the invasiveness of bladder cancer cells.

27. Role of TNTs:
• TNTs play important role in:
• Signal transduction.
• Immune responses.
• Micro and nano-particles delivery.
• Embryogenesis and development.
• Cancer Initiation and progression.
• Pathogens transfer.

29. TNTs role in mRNA transfer:
• RNAs have been shown to undergo transfer
between mammalian cells.
• Numerous publications have suggested that
RNAs undergo transfer via cytoplasmic
extensions, called membrane nanotubes.
• Membrane nanotubes connect donner and
acceptor cells.
• Examples are mouse B-actin and human cyclin
D1.

30. TNT communication between bacterial
cells:
• In 2006 Bassler and Losick demonstrated that
bacterial cells communicate via Tunneling
nanotubes.
• They used Bacillus subtilis as a model
organism.
• They demonstrated that non-conjugative
plasmids could be transferred from one cell to
another.